Acylsemicarbazides as cyclin dependent kinase inhibitors useful as anti-cancer and anti-proliferative agents

ABSTRACT

The present invention relates to the synthesis of a new class of indeno[1,2-c]pyrazol-4-ones of formula (I):                    
     that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-7 and their regulatory subunits know as cyclins A-G. 
     This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of U.S. Ser. No.09/692,023, Filed Oct. 19, 2000, entitled “ACYLSEMICARBAZIDES AND THEIRUSES”, now U.S. Pat. No. 6,291,504, which is a non-provisional filing ofprovisional application 60/160,713, filed Oct. 20, 1999, entitled“ACYLSEMICARBAZIDES AS CYCLIN DEPENDENT KINASE INHIBITORS USEFUL ASANTI-CANCER AND ANTI-PROLIFERATIVE AGENTS” which applications are hereinincorporated by reference in their entirity as though set forth in full.

FIELD OF THE INVENTION

This invention relates generally to novel5-substituted-indeno[1,2-c]pyrazol-4-ones which are useful as cyclindependent kinase (cdk) inhibitors, pharmaceutical compositionscomprising the same, methods for using the same for treatingproliferative diseases, and intermediates and processes for making thesame.

BACKGROUND OF THE INVENTION

One of the most important and fundamental processes in biology is thedivision of cells mediated by the cell cycle. This process ensures thecontrolled production of subsequent generations of cells with definedbiological function. It is a highly regulated phenomenon and responds toa diverse set of cellular signals both within the cell and from externalsources. A complex network of tumor promoting and suppressing geneproducts are key components of this cellular signaling process. Overexpression of the tumor promoting components or the subsequent loss ofthe tumor suppressing products will lead to unregulated cellularproliferation and the generation of tumors (Pardee, Science 246:603-608,1989).

Cyclin dependent kinases (cdks) play a key role in regulating the cellcycle machinery. These complexes consist of two components: a catalyticsubunit (the kinase) and a regulatory subunit (the cyclin). To date, sixkinase subunits (cdk 1-7) have been identified along with severalregulatory subunits (cyclins A-H). Each kinase associates with aspecific regulatory partner and together make up the active catalyticmoiety. Each transition of the cell cycle is regulated by a particularcdk complex: G1/S by cdk2/cyclin E, cdk4/cyclin D1 and cdk6/cyclinD/2;S/G2 by cdk2/cyclin A and cdk1/cyclin A; G2/M by cdk1/B. The coordinatedactivity of these kinases guides the individual cells through thereplication process and ensures the vitality of each subsequentgeneration (Sherr, Cell 73:1059-1065, 1993; Draetta, Trends Biochem.Sci. 15:378-382, 1990)

An increasing body of evidence has shown a link between tumordevelopment and cdk related malfunctions. Over expression of the cyclinregulatory proteins and subsequent kinase hyperactivity have been linkedto several types of cancers (Jiang, Proc. Natl. Acad. Sci. USA90:9026-9030, 1993; Wang, Nature 343:555-557, 1990). More recently,endogenous, highly specific protein inhibitors of cdks were found tohave a major affect on cellular proliferation (Kamb et al, Science264:436-440, 1994; Beach, Nature 336:701-704, 1993). These inhibitorsinclude p16^(INK4) (an inhibitor of cdk4/D1), p21^(CIP1) (a general cdkinhibitor), and p27^(KIP1) (a specific cdk2/E inhibitor). A recentcrystal structure of p27 bound to cdk2/A revealed how these proteinseffectively inhibit the kinase activity through multiple interactionswith the cdk complex (Pavletich, Nature 382:325-331, 1996). Theseproteins help to regulate the cell cycle through specific interactionswith their corresponding cdk complexes. Cells deficient in theseinhibitors are prone to unregulated growth and tumor formation.

This body of evidence has led to an intense search for small moleculeinhibitors of the cdk family as an approach to cancer chemotherapy.

A series of indeno[1,2-c]pyrazoles having anticancer activity aredescribed in JP 60130521 and JP 62099361 with the following genericstructure:

A series of indeno[1,2-c]pyrazoles having herbicidal activity aredescribed in GB 2223946 with the following generic structure:

A series of1-(6′-substituted-4′-methylquinol-2′-yl)-3-methylindeno[1,2-c]pyrazoleshaving CNS activity are described by Quraishi, Farmaco 44:753-8, 1989with the following generic structure:

There is a continuing unmet need for cdk inhibitors with which to treatproliferative diseases.

SUMMARY OF THE INVENTION

The present invention describes a novel class ofindeno[1,2-c]pyrazol-4-ones or pharmaceutically acceptable salt formsthereof that are potent inhibitors of the class of enzymes known ascyclin dependent kinases, which relate to the catalytic subunits cdk 1-7and their regulatory subunits know as cyclins A-H.

The present invention is also directed to a novel method of treatingcancer or other proliferative diseases by administering atherapeutically effective amount of one of these compounds or apharmaceutically acceptable salt form thereof.

A novel method of treating cancer or other proliferative diseases, whichcomprises administering a therapeutically effective combination of oneof the compounds of the present invention and one or more other knownanti-cancer or anti-proliferative agents is also described herein.

The present invention also describes compounds of formula (I):

wherein R₁, R₂ and X are defined below or pharmaceutically acceptablesalts thereof as cyclin dependent kinase inhibitors.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The invention pertains to novel cyclin dependent kinase inhibitors(cdks) and specifically, but not exclusively, as inhibitors ofcdk/cyclin complexes. The inhibitors of this invention areindeno[1,2-c]pyrazol-4-one analogs. Certain analogs were selective fortheir activity against cdks and their cyclin bound complexes and wereless active against other known serine/threonine kinases such as ProteinKinase A (PKA) and Protein Kinase C (PKC). In addition, these inhibitorswere less active against tyrosine kinases such as c-Ab1.

As described herein, the inhibitors of this invention are capable ofinhibiting the cell-cycle machinery and consequently would be useful inmodulating cell-cycle progression, which would ultimately control cellgrowth and differentiation. Such compounds would be useful for treatingsubjects having disorders associated with excessive cell proliferation,such as the treatment of cancer, psoriasis, immunological disordersinvolving unwanted leukocyte proliferation, in the treatment ofrestinosis and other smooth muscle cell disorders, and the like.

The present invention, in a first embodiment, describes a novel compoundof formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein:

X is selected from the group: O, S, and NR;

R is selected from the group: H, C₁₋₄ alkyl, and NR⁵R^(5a);

R¹ is selected from the group: H, C₁₋₁₀ alkyl substituted with 0-3R^(c), C₂₋₁₀ alkenyl substituted with 0-3 R^(c), C₂₋₁₀ alkynylsubstituted with 0-3 R^(c), C₁₋₁₀ alkoxy, —NHR⁴, C₃₋₁₀ carbocyclesubstituted with 0-5 R^(a), and 3-10 membered heterocycle containingfrom 1-4 heteroatoms selected from O, N, and S and substituted with 0-5R^(b);

R² is selected from the group: H, C₁₋₁₀ alkyl substituted with 0-3R^(c), C₂₋₁₀ alkenyl substituted with 0-3 R^(c), C₂₋₁₀ alkynylsubstituted with 0-3 R^(c), —(CF₂)_(m)CF₃, C₃₋₁₀ carbocycle substitutedwith 0-5 R^(a), and 3-10 membered heterocycle containing from 1-4heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R³ is selected from the group: H, halo, —CN, NO₂, C₁₋₄ haloalkyl,NR⁵R^(5a), NR⁵NR⁵R^(5a), NR⁵C(O)OR⁵, NR⁵C(O)R⁵, ═O, OR⁵, COR⁵, CO₂R⁵,CONR⁵R^(5a), NHC(O)NR⁵R^(5a), NHC(S)NR⁵R^(5a), SO₂NR⁵R^(5a), SO₂R^(5b),C₁₋₄ alkyl, phenyl, benzyl, C₁₋₄ alkyl substituted with 1-3 R^(c), C₅₋₁₀alkyl substituted with C₂₋₁₀ alkenyl optionally substituted with 0-3 R⁶,C₂₋₁₀ alkynyl substituted with 0-3 R⁶, —(CF₂)_(m)CF₃, C₃₋₁₀ carbocyclesubstituted with 0-5 R⁶, and 5-10 membered heterocycle containing from1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R⁶; and

provided that if R³ is phenyl, it is substituted with 1-5 R^(a);

R⁴ is independently at each occurrence selected from the group: H, —CN,C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³,CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a),SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10membered heterocycle containing from 1-4 heteroatoms selected from O, N,and S, substituted with 0-3 R³;

provided that at least one R³ is present and that this R³ is selectedfrom the group: C₁₋₄ alkyl substituted with 1-3 R⁶, C₅₋₁₀ alkylsubstituted with C₂₋₁₀ alkenyl optionally substituted with 0-3 R⁶, C₂₋₁₀alkynyl substituted with 0-3 R⁶, —(CF₂)_(m)CF₃, C₃₋₁₀ carbocyclesubstituted with 0-5 R⁶, and 5-10 membered heterocycle containing from1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R⁶;

R^(a) is independently at each occurrence selected from the group: halo,—CN, N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), ═O, OR³, COR³,CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), NR³C(O)OR³,NR³C(O)R³, SO₂NR³R^(3a), SO₂R^(3b), and 5-10 membered heterocyclecontaining from 1-4 heteroatoms selected from O, N, and S;

alternatively, when two R², are present on adjacent carbon atoms theycombine to form —OCH₂O— or —OCH₂CH₂O—;

R^(b) is independently at each occurrence selected from the group: halo,—CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³,OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a),SO₂NR³R^(3a), and SO₂R^(3b);

R^(c) is independently at each occurrence selected from the group: halo,—CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR⁵NR⁵R^(5a),NR³C(O)OR³, NR³C(O)R³, ═O, OR³, COR³, CO₂R³, CONR³R^(3a),NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocyclecontaining from 1-4 heteroatoms selected from O, N, and S, substitutedwith 0-3 R³;

R^(3a) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to whichthey are attached, form a heterocycle having 4-8 atoms in the ringcontaining an additional 0-1 N, S, or O atom and substituted with 0-3R^(3c);

R^(3b) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

R^(3c) is independently at each occurrence selected from the group:halo, —CN, N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3b), ═O, OR³,COR³, CO₂R³, CONR³R³ ^(b) , NHC(O)NR³R³ ^(b) , NHC(S)NR³R³ ^(b) ,NR³C(O)OR³, NR³C(O)R³, SO₂NR³R³ ^(b) , SO₂R^(3b), and 5-10 memberedheterocycle containing from 1-4 heteroatoms selected from O, N, and S;

R⁵ is independently selected from the group: H, C₁₋₄ alkyl, phenyl andbenzyl;

R^(5a) is independently selected from the group: H, C₁₋₄ alkyl, phenyland benzyl;

R^(5b) is independently selected from the group: H, C₁₋₄ alkyl, phenyland benzyl;

R⁶ is independently at each occurrence selected from the group: halo,—CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR⁵R⁵, NR⁵NR⁵R^(5a), NR⁵C(O)OR⁵,NR⁵C(O)R⁵, ═O, OR⁵, COR⁵, CO₂R⁵, CONR⁵R^(5a), NHC(O)NR⁵R^(5a),NHC(S)NR⁵R^(5a), SO₂NR⁵R^(5a), SO₂R^(5b), C₃₋₁₀ carbocycle substitutedwith 0-5 R⁵, and 5-10 membered heterocycle containing from 1-4heteroatoms selected from O, N, and S, substituted with 0-3 R⁵; and

m is selected from 0, 1, 2, and 3.

In another embodiment of the present invention, the compounds of formula(I) are selected from:

3-(4-methoxyphenyl)-5-(2-benzoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-isonicotinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-nictinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(3,4-dihydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5(2-(4-hydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(3-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(4-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(2-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(4-N,N-dimethylaminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-phenethylacetylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(2-(2-hydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;and

3-(4-methoxyphenyl)-5-(2-methoxycarbonylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one;

1-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-yl-urea;

[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea;

1-(2-amino-cyclohexyl)-3-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea;

2-(4-aminomethyl-piperidin-1-yl)-N-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide;

1-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-yl-urea.

or pharmaceutically acceptable salt form thereof.

Another embodiment of the present invention is a pharmaceuticalcomposition comprising: a pharmaceutically acceptable carrier and atherapeutically effective amount of a compound of formula (I).

Another embodiment of the present invention is a method of treatingcancer and proliferative diseases comprising: administering to a host inneed of such treatment a therapeutically effective amount of a compoundof formula (I), or a pharmaceutically effective salt form thereof.

DEFINITIONS

As used herein, the following terms and expressions have the indicatedmeanings. The compounds of the present invention may contain anasymmetrically substituted carbon atom, and may be isolated in opticallyactive or racemic forms. It is well known in the art how to prepareoptically active forms, such as by resolution of racemic forms or bysynthesis from optically active starting materials. All chiral,diastereomeric, racemic forms and all geometric isomeric forms of astructure are intended, unless the specific stereochemistry or isomerform is specifically indicated.

The term “alkyl” is intended to include both branched and straight-chainsaturated aliphatic hydrocarbon groups having the specified number ofcarbon atoms. Examples of alkyl include, but are not limited to, methyl,ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, ands-pentyl. In addition, the term is intended to include bothunsubstituted and substituted alkyl groups, the latter referring toalkyl moieties having one or more hydrogen substituents replaced by, butnot limited to halogen, hydroxyl, carbonyl, alkoxy, ester, ether, cyano,phosphoryl, amino, imino, amido, sulfhydryl, alkythio, thioester,sulfonyl, nitro, heterocyclo, aryl or heteroaryl. It will also beunderstood by those skilled in the art that the substituted moietiesthemselves can be substituted as well when appropriate.

The terms “halo” or “halogen” as used herein refer to fluoro, chloro,bromo and iodo. The term “aryl” is intended to mean an aromatic moietycontaining the specified number of carbon atoms, such as, but notlimited to phenyl, indanyl or naphthyl. The terms “cycloalkyl” and“bicycloalkyl” are intended to mean any stable ring system, which may besaturated or partially unsaturated. Examples of such include, but arenot limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl,bicyclo[2.2.2]nonane, adamantly, or tetrahydronaphthyl (tetralin).

As used herein, “carbocycle” or “carbocyclic residue” is intended tomean any stable 3- to 7-membered monocyclic or bicyclic or 7- to13-membered bicyclic or tricyclic, any of which may be saturated,partially unsaturated, or aromatic. Examples of such carbocyclesinclude, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, adamantyl, cyclooctyl,; [3.3.0]bicyclooctane,[4.3.0]bicyclononane, [4.4.0]bicyclodecane (decalin),[2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl,or tetrahydronaphthyl (tetralin).

As used herein, the term “heterocycle” or “heterocyclic system” isintended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7-to 10-membered bicyclic heterocyclic ring which is saturated partiallyunsaturated or unsaturated (aromatic), and which consists of carbonatoms and from 1 to 4 heteroatoms independently selected from the groupconsisting of N, O and S and including any bicyclic group in which anyof the above-defined heterocyclic rings is fused to a benzene ring. Thenitrogen and sulfur heteroatoms may optionally be oxidized. Theheterocyclic ring may be attached to its pendant group at any heteroatomor carbon atom which results in a stable structure. The heterocyclicrings described herein may be substituted on carbon or on a nitrogenatom if the resulting compound is stable. If specifically noted, anitrogen in the heterocycle may optionally be quaternized. It ispreferred that when the total number of S and O atoms in the heterocycleexceeds 1, then these heteroatoms are not adjacent to one another. It ispreferred that the total number of S and O atoms in the heterocycle isnot more than 1. As used herein, the term “aromatic heterocyclic system”is intended to mean a stable 5- to 7-membered monocyclic or bicyclic or7- to 10-membered bicyclic heterocyclic aromatic ring which consists ofcarbon atoms and from 1 to 4 heterotams independently selected from thegroup consisting of N, O and S. It is preferred that the total number ofS and O atoms in the aromatic heterocycle is not more than 1.

Examples of heterocycles include, but are not limited to, 1H-indazole,2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl,4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl,acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl,carbazolyl, 4aH-carbazolyl, b-carbolinyl, chromanyl, chromenyl,cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl,imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl,indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl,isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, oxazolidinyl., oxazolyl, oxazolidinylperimidinyl,phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl,phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl,piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl,purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl,pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl,pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl,quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl,tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl,6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl,thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl,triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl, xanthenyl. Preferred heterocycles include, but are notlimited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl,imidazolyl, indolyl, benzimidazolyl, 1H-indazolyl, oxazolidinyl,benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, or isatinoyl.Also included are fused ring and spiro compounds containing, forexample, the above heterocycles.

As used herein, “pharmaceutically acceptable salts” refer to derivativesof the disclosed compounds wherein the parent compound is modified bymaking acid or base salts thereof. Examples of pharmaceuticallyacceptable salts include, but are not limited to, mineral or organicacid salts of basic residues such as amines; alkali or organic salts ofacidic residues such as carboxylic acids; and the like. Thepharmaceutically acceptable salts include the conventional non-toxicsalts or the quaternary ammonium salts of the parent compound formed,for example, from non-toxic inorganic or organic acids. For example,such conventional non-toxic salts include those derived from inorganicacids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric,nitric and the like; and the salts prepared from organic acids such asacetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric,citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic,benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric,toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic,and the like.

The pharmaceutically acceptable salts of the present invention can besynthesized from the parent compound which contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two; generally, nonaqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare preferred. Lists of suitable salts are found in Remington'sPharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa.,1990, p. 1445, the disclosure of which is hereby incorporated byreference.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complicationcommensurate with a reasonable benefit/risk ratio.

“Prodrugs”, as the term is used herein, are intended to include anycovalently bonded carriers which release an active parent drug of thepresent invention in vivo when such prodrug is administered to amammalian subject. Since prodrugs are known to enhance numerousdesirable qualities of pharmaceuticals (i.e., solubility,bioavailability, manufacturing, etc.) the compounds of the presentinvention may be delivered in prodrug form. Thus, the present inventionis intended to cover prodrugs of the presently claimed compounds,methods of delivering the same, and compositions containing the same.Prodrugs of the present invention are prepared by modifying functionalgroups present in the compound in such a way that the modifications arecleaved, either in routine manipulation or in vivo, to the parentcompound. Prodrugs include compounds of the present invention wherein ahydroxy, amino, or sulfhydryl group is bonded to any group that, whenthe prodrug of the present invention is administered to a mammaliansubject, it cleaves to form a free hydroxyl, free amino, or freesulfydryl group, respectively. Examples of prodrugs include, but are notlimited to, acetate, formate, and benzoate derivatives of alcohol andamine functional groups in the compounds of the present invention.

“Substituted” is intended to indicate that one or more hydrogens on theatom indicated in the expression using “substituted” is replaced with aselection from the indicated group(s), provided that the indicatedatom's normal valency is not exceeded, and that the substitution resultsin a stable compound. When a substituent is keto (i.e., ═O) group, then2 hydrogens on the atom are replaced.

As used herein, the term “anti cancer” or “anti-proliferative” agentincludes, but is not limited to, altretamine, busulfan, chlorambucil,cyclophosphamide, ifosfamide, mechlorethamine, melphalan, thiotepa,cladribine, fluorouracil, floxuridine, gemcitabine, thioguanine,pentostatin, methotrexate, 6-mercaptopurine, cytarabine, carmustine,lomustine, streptozotocin, carboplatin, cisplatin, oxaliplatin,iproplatin, tetraplatin, lobaplatin, JM216, JM335, fludarabine,aminoglutethimide, flutamide, goserelin, leuprolide, megestrol acetate,cyproterone acetate, tamoxifen, anastrozole, bicalutamide,dexamethasone, diethylstilbestrol, prednisone, bleomycin, dactinomycin,daunorubicin, doxirubicin, idarubicin, mitoxantrone, losoxantrone,mitomycin-c, plicamycin, paclitaxel, docetaxel, topotecan, irinotecan,9-amino camptothecan, 9-nitro camptothecan, GS-211, etoposide,teniposide, vinblastine, vincristine, vinorelbine, procarbazine,asparaginase, pegaspargase, octreotide, estramustine, hydroxyurea.

SYNTHESIS

The compounds of the present invention can be synthesized using themethods described below, together with synthetic methods known in theart of synthetic organic chemistry, or variations thereon as appreciatedby those skilled in the art. Preferred methods include, but are notlimited to, those methods described below. Each of the references citedbelow are hereby incorporated herein by reference.

An approach to preparing indeno[1,2-c]pyrazol-4-ones is presented inScheme 1 and can be used to prepare compounds of the present invention.The nitro group of dimethyl 3-nitrophthalate was reduced to the amineusing catalytic hydrogenation. The aniline was acylated using aceticanhydride and pyridine as a base. A mixture of the resulting acetamide 2and an acetophenone were treated with a strong base in an appropriatesolvent at elevated temperature to give the desired triketone 3.Additional means of preparing triketones are known to one skilled in theart as described in Kilgore et al, Industrial and Engineering Chemistry34:494-497, 1946, the contents of which are hereby incorporated hereinby reference. The triketone was treated with hydrazine at elevatedtemperature in an appropriate solvent to give theindeno[1,2-c]pyrazol-4-one ring system. Additional means of preparingindeno[1,2-c]pyrazol-4-ones are known to one skilled in the art asdescribed in Lemke et al., J. Heterocyclic Chem. 19:1335-1340, 1982;Mosher and Soeder, J. Heterocyclic Chem. 8:855-59, 1971; Hrnciar andSvanygova Collect. Czech. Chem. Commun. 59:2734-40, 1994 the contents ofwhich are hereby incorporated herein by reference. The amide wasdeacylated by heating with a strong acid in an appropriate solvent togive aniline 4. This aniline was acylated under standard conditionsusing an acid chloride in an appropriate solvent to give the desiredproduct 5.

An alternative method for making compounds of the present invention isshown in Scheme 2. The intermediate triketone 3 can be deacylated withstrong acid and reacylated with an appropriate acid chloride usingmethods known to those skilled in the art. Subsequently, triketone 6 canthe be converted to the indeno[1,2-c]pyrazol-4-one ring system using thesame conditions described previously in Scheme 1.

Another method for preparing the triketones 6 of Scheme 2 employs thecondensation of a 1,3-diketone 6a with 3-nitrophthalic anhydride asdescribed in Rotberg and Oshkaya, Zh. Organ. Khim. 8:84-87, 1972; Zh.Organ. Khim. 9:2548-2550, 1973, the contents of which are herebyincorporated herein by reference. The 1,3-diketones, when notcommercially available can be readily prepared by one skilled in the artby the acetylation or trifluoroacetylation of the requisite methylketone, R¹COCH₃. Reduction of the nitro derivative 6b to the aniline 6ccan be accomplished in a variety of ways including catalyichydrogenation, treatment with zinc or iron under acidic conditions, ortreatment with other reducing agents such as sodium dithionite orstannous chloride. Subsequently the aniline 6c can be converted to theindeno[1,2-c]pyrazol-4-ones of this invention by acylation followed bytreatment with hydrazine as described previously in Scheme 2.

Another method for making the indeno[1,2-c]pyrazol-4-one ring system isshown in Scheme 4. Dimethyl hydrazine was reacted with 3-acetylpyridinewith no solvent to give the hydrazone 7. This was treated in a similarfashion as described in Scheme 1 to give the desired intermediate 8.Additional means of preparing similar intermediates are known to oneskilled in the art as described in Rappoport, J. Org. Chem.49:2948-2953, 1984, the contents of which are hereby incorporated hereinby reference. This intermediate was carried through the sequence in asimilar fashion as described in Scheme 1.

Another approach to preparing indeno[1,2-c]pyrazol-4-ones is presentedin Scheme 5 and can be used to prepare compounds of the presentinvention. Treating the intermediate 5-aminoindeno[1,2-c]pyrazol-4-onewith 2-(trimethylsilyl) ethoxymethylmethyl chloride (SEMCl) and asuitable base in an inert solvent under reflux gives the SEM protectedintermediate. The aniline is converted to the carbamate withphenylchloroformate using methods known to those skilled in the art.This intermediate is reacted with carbaztes in DMSO at elevatedtemperatures and then the SEM group is removed by treating with acid ina polar protic solvent to give the desired acylsemicarbazide-containingindenopyrazole analogs.

Other features of the invention will become apparent during thefollowing descriptions of exemplary embodiments which are given forillustration of the invention and are not intended to be limitingthereof.

EXAMPLES

Abbreviations used in the Examples are defined as follows: “°C.” fordegrees Celsius, “CIMS” for chemical ionization mass spectroscopy, “eq”for equivalent or equivalents, “g” for gram or grams, “h” for hour orhours, “mg” for milligram or milligrams, “mL” for milliliter ormilliliters, “mmol” for millimolar, “M” for molar, “min” for minute orminutes, “p-TsOH” for para-toluenesulphonic acid, “DMF” fordimethylformamide, and “TFA” for trifluoroacetic acid.

Example I Preparation of3-(4-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 2 from Dimethyl 3-nitrophthalate.

A solution of dimethyl 3-nitrophthalate (25 g, 105 mmol) in methanol(100 mL) was treated with 5% Pd/C (2.5 g) and hydrogenated on a ParrShaker at 50 psi for 2 h. The solution was filtered (Celite), thefiltrate collected and the solvent removed at reduced pressure. Theresidue was dissolved in acetic anhydride (20 mL) treated with pyridine(0.05 mL) and heated to 80° C. for 1 min. The reaction was cooled andstirred at 25° C. for 2 h. The solvent was removed at reduced pressureand the residue recrystallized from ethanol to give the product as awhite solid (21 g, 79%). mp 104-105° C.; CIMS m/e calc'd for C₁₂H₁₄NO₅:252.0872, found 252.0888; Analysis calc'd for C₁₂H₁₃NO₅: C, 57.37; H,5.22; N, 5.58; found: C, 57.67; H, 5.29; N, 5.77.

Step 2. Synthesis of Triketone 11 from 2.

A solution of 2 (1 g, 4.0 mmol) in dry DMF (2 mL) was treated withsodium hydride (0.15 g, 60% suspension in oil, 0.4 mmol) in one portion.After 1 h, 4-methoxyacetophenone (0.6 g, 4.0 mmol) was added in oneportion and the reaction heated to 90° C. A second portion of sodiumhydride (0.15 g, 60% suspension in oil, 0.4 mmol) was added and theexothermic reaction turns deep red. After 20 min, the reaction wascooled to 25° C. diluted with water (20 mL), extracted with EtOAc (10mL) and the aqueous phase separated. The aqueous phase was acidifiedwith 2 N HCl to pH 2 and the crude product collected. Recrystalizationwith ethanol gave the desired product as a yellow solid (0.4 g, 30%). mp174-175° C.; CIMS m/e calc'd for C₁₉H₁₆NO₅: 338.1028, found 338.1022;Analysis calc'd for C₁₉H₁₅NO₅: C, 67.65; H, 4.48; N, 4.15; found: C,67.87; H, 4.29; N, 3.99.

Step 3. Synthesis of 12 from 11.

A solution of 11 (0.2 g, 0.6 mmol) in EtOH (5 mL) was treated withhydrazine hydrate (0.1 mL, 1.8 mmol) and p-TsOH (3 mg). The reaction washeated to reflux and stirred for 2 h. The reaction was cooled to 25° C.and the product collected as a yellow solid (0.1 g, 50%). mp 268° C.;CIMS m/e calc'd for C₁₉H₁₆N₃O₃: 334.1192, found: 334.1168; Analysiscalc'd for C₁₉H₁₅N₃O₃: C, 68.46; H, 4.54; N, 12.61; found: C, 68.81; H,4.39; N, 12.45.

Example II Preparation of3-(4-methoxyphenyl)-5-(chloroacetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 13 from 12.

A suspension of 12 (1.0 g, 3.0 mmol) in MeOH (10 mL) was treated withconc. HCl (1 mL) and heated to reflux. After 2 h, the reaction wascooled and the product was collected as a greenish solid (0.7 g, 81%).mp 273° C.; CIMS m/e calc'd for C₁₇H₁₃N₃O₂:292.1086, found: 292.1080;Analysis calc'd for C₁₇H₁₄N₃O₂: C, 69.85; H, 4.83; N, 14.37; found: C,69.99; H, 4.59; N, 14.44.

Step 2. Synthesis of 14 from 13.

A suspension of 13 (20 mg, 0.07 mmol) in dioxane (2 mL) was treated withaqueous sat. NaHCO₃ (1 mL) and chloroacetyl chloride (30 mL, 0.21 mmol).The reaction was heated to 50° C. and stirred for 2 h. The reaction wascooled, poured into water (2 mL), extracted with EtOAc (10 mL), theorganic layer separated, dried (MgSO₄) and the solvent removed atreduced pressure. The solid residue was recrystallized from EtOH to givethe product as a yellow solid (9 mg, 35%). mp 274° C.; CIMS m/e calc'dfor C₁₉H₁₅N₃O₃Cl: 368.0802, found: 368.0818.

Example III Preparation of3-(4-methoxyphenyl)-5-(cyclopropylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II usingcyclopropylacetyl chloride as the starting material. mp 289° C.; CIMSm/e calc'd for C₂₁H₁₈N₃O₃: 360.1348, found: 360.1330.

Example IV Preparation of3-(4-methoxyphenyl)-5-(isopropylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II usingisopropylacetyl chloride as the starting material. mp 288° C.; CIMS m/ecalc'd for C₂₁H₂₀N₃O₃: 362.1505, found: 362.1535.

Example V Preparation of3-(4-methoxyphenyl)-5-(ethylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II usingpropionyl chloride as the starting material. mp 287 ° C.; CIMS m/ecalc'd for C₂₀H₁₈N₃O₃: 348.1348, found: 348.1313.

Example VI Preparation of3-(4-methoxyphenyl)-5-(cyclopentylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II usingcyclopentylacetyl chloride as the starting material. mp 267° C.; CIMSm/e calc'd for C₂₃H₂₂N₃O₃: 388.1661, found: 388.1626.

Example VII Preparation of3-(4-methoxyphenyl)-5-(cyclobutylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II usingcyclobutylacetyl chloride as the starting material. mp 297° C.; CIMS m/ecalc'd for C₂₂H₂₀N₃O₃: 374.1505, found: 374.1530.

Example VIII Preparation of3-(4-methoxyphenyl)-5-(phenylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II usingphenylacetyl chloride as the starting material. mp 280° C.; CIMS m/ecalc'd for C₂₅H₂₀N₃O₃: 410.1505, found: 410.1533.

Example IX Preparation of3-(4-methoxyphenyl)-5-(butylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using butyrylchloride as the starting material. mp 282° C.; CIMS m/e calc'd forC₂₁H₂₀N₃O₃: 362.1505, found: 362.1500.

Example X Preparation of3-(4-methoxyphenyl)-5-((4-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using4-chlorophenylacetyl chloride as the starting material. mp 238° C.; CIMSm/e calc'd for C₂₅H₁₉N₃O₃Cl: 444.1115, found: 444.1110.

Example XI Preparation of3-(4-methoxyphenyl)-5-((3-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using3-methoxyphenylacetyl chloride as the starting material. mp >300° C.;CIMS m/e calc'd for C₂₆H₂₂N₃O₄: 440.1610, found: 440.1620.

Example XII Preparation of3-(4-methoxyphenyl)-5-((4-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using4-methoxyphenylacetyl chloride as the starting material. mp 280° C.;CIMS m/e calc'd for C₂₆H₂₂N₃O₄: 440.1610, found: 440.1630.

Example XIII Preparation of3-(4-methoxyphenyl)-5-((3,4-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using3,4-dimethoxyphenylacetyl chloride as the starting material. mp >300°C.; CIMS m/e calc'd for C₂₇H₂₄N₃O₅: 470.1716, found: 470.1731.

Example XIV Preparation of3-(4-methoxyphenyl)-5-((2,5-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using2,5-dimethoxyphenylacetyl chloride as the starting material. mp 226° C.;CIMS m/e calc'd for C₂₇H₂₄N₃O₅: 470.1716, found: 470.1739.

Example XV Preparation of3-(2-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using2-methoxyacetophenone as the starting material. mp 276° C.; CIMS m/ecalc'd for C₁₉H₁₆N₃O₃: 334.1192, found: 334.1169.

Example XVI Preparation of3-(3,4-dimethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using3,4-dimethoxyacetophenone as the starting material. mp >300° C.; CIMSm/e calc'd for C₂₀H₁₈N₃O₄: 364.1297, found: 364.1288.

Example XVII Preparation of3-(4-methoxyphenyl)-5-((3,4-ethylenedioxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 15 from 11.

A suspension of 11 (5 g, 14.8 mmol) in MeOH (50 mL) was treated withconc. HCl (3 mL) and heated to reflux. After stirring for 2 h, thereaction was cooled to 0° C. and the product collected as a yellow solid(4.2 g, 96%). mp 173° C.; CIMS m/e calc'd for C₁₇H₁₄NO₄: 296.0923,Found: 296.0901.

Step 2. Synthesis of 16 from 15.

A suspension of 15 (20 mg, 0.07 mmol) in acetone (2 mL) was treated withNaHCO₃ (10 mg) and the acid chloride of (3,4-methylenedioxyphenyl)aceticacid (prepared by heating the acid in a benzene:thionyl chloride 4:1mixture at 50° C. for 2 h, removing the volatile components at reducedpressure, and using the crude acid chloride without furtherpurification). The reaction was heated to 50° C. and stirred for 2 h.The reaction was cooled, poured into water (4 mL), extracted with EtOAc(10 mL), dried (MgSO₄), filtered and concentrated. The crude triketonewas suspended in EtOH (2 mL), treated with hydrazine hydrate (0.05 mL)and p-TsOH (1 mg) and heated to reflux for 2 h. The reaction was cooledto 0° C. and the product filtered to give a yellow solid (6.5 mg, 20%).mp 297° C.; CIMS m/e calc'd for C₂₆H₂₀N₃O₅: 454.1403, Found: 454.1398.

Example XVIII Preparation of3-(4-dimethoxyphenyl)-5-((3-thiophene)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using theacid chloride of 3-thiopheneacetic acid as the starting material. mp293° C.; CIMS m/e calc'd for C₂₃H₁₈N₃O₃S: 416.1069, found: 416.1088.

Example XIX Preparation of3-(4-methoxyphenyl)-5-((2-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using theacid chloride of 2-methoxyphenylacetic acid as the starting material. mp255° C.; CIMS m/e calc'd for C₂₆H₂₂N₃O₄: 440.1610, found: 440.1622.

Example XX Preparation of3-(4-methoxyphenyl)-5-((3,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using theacid chloride of 3,4-dichlorophenylacetic acid as the starting material.mp 299° C.; CIMS m/e calc'd for C₂₅H₁₈N₃O₃Cl₂: 478.0725, found:478.0744.

Example XXI Preparation of3-(4-methoxyphenyl)-5-((2,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using theacid chloride of 2,4-dichlorophenylacetic acid as the starting material.mp 286° C.; CIMS m/e calc'd for C₂₅H₁₈N₃O₃Cl₂: 478.0725, found:478.0734.

Example XXII Preparation of3-(4-methoxyphenyl)-5-((2-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using theacid chloride of 2-chlorophenylacetic acid as the starting material. mp300° C.; CIMS m/e calc'd for C₂₅H₁₉N₃O₃Cl: 444.1115, found: 444.1111.

Example XXIII Preparation of3-(4-methoxyphenyl)-5-(aminoacetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 14 (15 mg, 0.04 mmol) in EtOH (1 mL) was treated withconc. NH₄OH (1 mL), placed in a sealed tube and heated to 80° C. for 3h. The reaction was cooled and the solvent removed at reduced pressure.The residue was recrystallized from EtOH to give the product as a yellowsolid (9 mg, 62%). mp >300° C.; CIMS m/e calc'd for C₂₀H₁₉N₄O₃:363.1457, Found: 363.1431.

Example XXIV Preparation of3-(4-methoxyphenyl)-5-((2-hydroxyethyl)aminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usinghydroxylamine as the starting material. mp 243° C.; CIMS m/e calc'd forC₂₁H₂₁N₄O₄: 393.1563, found: 393.1539.

Example XXV Preparation of3-(4-methoxyphenyl)-5-(N,N-dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingdimethylamine as the starting material. mp 279° C.; CIMS m/e calc'd forC₂₁H₂₁N₄O₃: 377.1614, found: 377.1640.

Example XXVI Preparation of3-(4-methoxyphenyl)-5-(piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingpiperazine as the starting material. mp 277° C.; CIMS m/e calc'd forC₂₃H₂₄N₅O₃: 418.1879, found: 418.1899.

Example XXVII Preparation of3-(4-methoxyphenyl)-5-(4-methylpiperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-methylpiperizine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₄H₂₆N₅O₃: 432.2036, found: 432.2030.

Example XXVIII Preparation of3-(4-methoxyphenyl)-5-(4-(2-hydroxyethyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-hydroxyethylpiperizine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₅H₂₈N₅O₄: 462.2141, found: 462.2128.

Example XXIX Preparation of3-(4-methoxyphenyl)-5-(piperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingpiperidine as the starting material. mp 291° C.; CIMS m/e calc'd forC₂₄H₂₅N₄O₃: 417.1927, found: 417.1955.

Example XXX Preparation of3-(4-methoxyphenyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-aminomethylpiperidine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₅H₂₈N₅O₃: 446.2192, found: 446.2166.

Example XXXI Preparation of3-(4-methoxyphenyl)-5-(ethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingethylamine as the starting material. mp 250° C.; CIMS m/e calc'd forC₂₁H₂₁N₄O₃: 377.1614, found: 377.1644.

Example XXXII Preparation of3-(4-methoxyphenyl)-5-(thiomorpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingthiomorpholine as the starting material. mp 298° C.; CIMS m/e calc'd forC₂₃H₂₃N₄O₃S: 435.1491, found: 435.1477.

Example XXXIII Preparation of3-(4-methoxyphenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingmorpholine as the starting material. mp 295° C.; CIMS m/e calc'd forC₂₃H₂₃N₄O₄: 419.1719, found: 419.1744.

Example XXXIV Preparation of3-(4-methoxyphenyl)-5-(pyrrolidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingpyyrolidine as the starting material. mp 279° C.; CIMS m/e calc'd forC₂₃H₂₃N₄O₃: 403.1770, found: 403.1761.

Example XXXV Preparation of3-(4-methoxyphenyl)-5-(4-pyridinylaminomethylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-aminomethylpyridine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₅H₂₂N₅O₃: 440.1723, found: 440.1762.

Example XXXVI Preparation of3-(4-methoxyphenyl)-5-((4-acetamidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 18 (10 mg, 0.02 mmol) in dioxane (1 mL) was treated withaqueous sat. NaHCO₃ (0.5 mL) and acetyl chloride (0.01 mL) and heated at50° C. for 1 h. The reaction was cooled, poured into water (5 mL),extracted with EtOAc (10 mL), the organic layer separated, dried (MgSO₄)and the solvent removed at reduced pressure. The residue wasrecrystallized from EtOH to give the product as a yellow solid (5.6 mg,61%). mp 268° C.; CIMS m/e calc'd for C₂₇H₂₃N₄O₄: 467.1719, Found:467.1730.

Example XXXVII Preparation of3-(4-methoxyphenyl)-5-((4-methoxycarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXXII usingmethylchloroformate as the starting material. mp 257° C.; CIMS m/ecalc'd for C₂₇H₂₃N₄O₅: 483.1668, found: 483.1633.

Example XXXVIII Preparation of3-(4-methoxyphenyl)-5-((4-aminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII and XXXIIusing chloroacetyl chloride and conc. NH₄OH as the starting materias. mp228° C.; CIMS m/e calc'd for C₂₇H₂₄N₅O₄: 482.1828, found: 482.1844.

Example XXXIX Preparation of3-(4-methoxyphenyl)-5-((4-N,N-dimethylaminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII and XXXIIusing chloroacetyl chloride and dimethyl amine as the starting materias.mp >300° C.; CIMS m/e calc'd for C₂₉H₂₈N₅O₄: 510.2141, found: 510.2121.

Example XL Preparation of3-(4-methoxyphenyl)-5-((4-azidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

A solution of example XXXVI (20 mg, 0.04 mmol) in DMF (2 mL) was treatedwith 5% palladium on carbon (5 mg) and hydrogentaed at atmosphericpressure using a hydrogen baloon. After 2 h, the solution was filtered(Celite), and the solvent removed at reduced pressure. The residue wasrecrystallized from EtOH to give the product as a yellow solid (15 mg,78%). mp >300° C.; CIMS m/e calc'd for C₂₅H₁₉N₆O₃: 451.1519, found:451.1544.

Example XLI Preparation of3-(4-methoxyphenyl)-5-((4-aminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXVII using theacid chloride of 4-azidophenylacetic acid as the starting material. mp283° C.; CIMS m/e calc'd for C₂₅H₂₁N₄O₃: 425.1614, found: 425.1643.

Example XLII Preparation of3-(4-methoxyphenyl)-5-(phenylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 20 from 15.

A suspension of 15 (0.5 g, 1.7 mmol) in acetone (10 mL) was treated withNaHCO₃ (0.5 g) and phenyl chloroformate. The mixture was heated to 50°C. for 2 h. The reaction was cooled, poured into water (20 mL),extracted with EtOAc (40 mL), the organic layer separated, dried (MgSO₄)and the solvent removed at reduced pressure. The residue was suspendedin EtOH (10 mL) and treated with hydrazine hydrate (0.16 mL, 5.1 mmol)and p-TsOH (10 mg). The mixture was heated to reflux and stirred for 3h. The reaction was cooled to 0° C. and the product collected as ayellow solid (0.25 g, 36%). mp 195° C.; CIMS m/e calc'd for C₂₄H₁₈N₃O₄:412.1297, Found: 412.1308.

Step 2. Synthesis of 21 from 20.

A solution of 20 (20 mg, 0.05 mmol) in DMSO (2 mL) was treated withaniline (20 mL, mmol) and dimethylaminopyridine (1 mg). The mixture washeated to 80° C. for 2 h. The reaction was cooled, poured into water (4mL), extracted with EtOAc (15 mL), the organic layer separated, dried(MgSO₄) and the solvent removed at reduced pressure. The residue wasrecrystallized from EtOH to give the product as a yellow solid (9 mg,44%). mp >300° C.; CIMS m/e calc'd for C₂₄H₁₉N₄O₃: 411.1457, Found:411.1432.

Example XLIII Preparation of3-(4-methoxyphenyl)-5-(butylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using butylamine as the starting material. mp 252° C.; CIMS m/e calc'd forC₂₁H₂₁N₄O₃: 377.1614, found: 377.1633.

Example XLIV Preparation of3-(4-methoxyphenyl)-5-(4-aminobenzylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using4-aminobenzyl amine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₅H₂₂N₅O₃: 440.1723, found: 440.1700.

Example XLV Preparation of3-(4-methoxyphenyl)-5-(4-pyridylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using4-aminomethylpyridine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₄H₂₀N₅O₃: 426.1566, found: 426.1533.

Example XLVI Preparation of3-(4-hydroxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 12 (20 mg, 0.07 mmol) in CH₂Cl₂ (2 mL) was treated withexcess BBr₃ (1.0 mL, 1.0 M in CH₂Cl₂) and stirred for 20 h. The reactionwas slowly poured into aqueous sat. NaHCO₃ (5 mL), extracted with EtOAc(10 mL), dried (MgSO₄) and concentrated. The residue was recrystallizedfrom EtOH to give the desired product as a yellow solid (7.5 mg, 33%).mp >300° C.; CIMS m/e calc'd for C₁₈H₁₄N₃O₃: 320.1035, Found: 320.1050.

Example XLVII Preparation of3-(4-methoxyphenyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one

A suspension of 13 (20 mg, 0.06 mmol) in formic acid (2 mL) was heatedto 100° C. for 2 h. The reaction mixture was cooled and the solventremoved at reduced pressure. The residue was recrystallized from EtOH togive the desired product as a yellow solid (12 mg, 63%). mp 280° C.;CIMS m/e calc'd for C₁₈H₁₄N₃O₃: 320.1035, Found: 320.1040.

Example XLVIII Preparation of3-(3-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 24 from 3-acetylpyridine.

A solution of 3-acetylpyridine (1.0 g, 8.3 mmol) in benzene (3 mL) wastreated with 1,1-dimethylhydrazine (0.62 mL, 8.3 mmol) and p-TsOH (5mg). The mixture was heated to 85° C. and stirred for 3 h. The reactionwas cooled and the solvent removed at reduced pressure. This crudehydrazone was treated with 1.0 M NaN(TMS)₂ in THF (16.6 mL, 16.6 mmol)at 25° C. over 5 min. After 30 min dimethyl 3-acetamidophthalate (2.1 g,8.3 mmol) was added in one portion and the reaction heated to reflux.Stirring was continued for 6 h. The reaction was cooled and quenched bythe slow addition of TFA. The solvent was removed at reduced pressureand the residue chromatographed (silica, 2.5-5% MeOH/CH₂Cl₂) to give theproduct as a yellow solid (0.35 g, 14%). mp 265° C.; CIMS m/e calc'd forC₁₇H₁₃N₂O₄: 309.0875, Found: 309.0888.

Step 2. Synthesis of 25 from 24.

A suspension of 24 (30 mg, 0.09 mmol) in EtOH (2 mL) was treated withhydrazine hydrate (0.05 mL) and p-TsOH (1 mg) and heated to reflux.After stirring for 2 h. the reaction was cooled and the product filteredto give a yellow solid (12 mg, 44%). mp >300° C.; CIMS m/e calc'd forC₁₇H₁₃N₄O₂: 305.1039, Found: 305.1048.

Example XLIX Preparation of3-(4-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLVIII using4-acetylpyridine as the starting material. mp >300° C.; CIMS m/e calc'dfor C₁₇H₁₃N₄O₂: 305.1039, found: 305.1046.

Example L Preparation of3-(4-pyridyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLVII using4-acetylpyridine as the starting material. mp >300° C.; CIMS m/e calc'dfor C₁₆H₁₁N₄O₂: 291.0882, found: 291.0882.

Example LI Preparation of3-phenyl-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I usingacetophenone as the starting material. mp >300° C.; CIMS m/e calc'd forC₁₈H₁₃N₃O₂: 304.1065, found: 304.1086.

Example LII Preparation of3-(4-methylthiophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-methylthioacetophenone as the starting material. mp 283° C.; CIMS m/ecalc'd for C₁₉H₁₅N₃O₂S: 350.0956, found: 350.0963.

Example LIII Preparation of3-(4-methylsulphonylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared by oxidation of the product of example LII. mp >300° C.; CIMSm/e calc'd for C₁₉H₁₅N₃O₄S: 382.0860, found: 382.0862.

Example LIV Preparation of3-(4-N,N-dimethylaminophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-N,N,-dimethylaminoacetophenone as the starting material. mp >300° C.;CIMS m/e calc'd for C₂₀H₁₈N₄O₂: 347.1496, found: 347.1508.

Example LV Preparation of3-(4-N,N-dimethylaminophenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LIV and morpholine as the startingmaterials. mp >300° C.; CIMS m/e calc'd for C₂₄H₂₆N₅O₃: 432.2036, found:432.2020.

Example LVI Preparation of3-(4-N,N-dimethylaminophenyl)-5-(dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LIV and dimethylamine as the startingmaterials. mp >300° C.; CIMS m/e calc'd for C₂₂H₂₄N₅O₂: 390.1930, found:390.1948.

Example LVII Preparation of3-(4-(1-piperidinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-(1-piperidinyl)acetophenone as the starting material. mp 291° C.;CIMS m/e calc'd for C₂₃H₂₂N₄O₂: 387.1801, found: 387.1821.

Example LVIII Preparation of3-(4-morpholinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-morpholinylacetophenone as the starting material. mp >300° C.; CIMSm/e calc'd for C₂₂H₂₀N₄O₃: 388.1528, found: 388.1535.

Example LIX Preparation of3-(4-ethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-ethoxyacetophenone as the starting material. mp 288° C.; CIMS m/ecalc'd for C₂₀H₁₇N₃O₃: 348.1325, found: 348.1348.

Example LX Preparation of3-(4-butylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-butylacetophenone as the starting material. mp 259° C.; CIMS m/ecalc'd for C₂₂H₂₁N₃O₂: 360.1701, found: 360.1712.

Example LXI Preparation of3-(4-ethylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-ethylacetophenone as the starting material. mp 294° C.; CIMS m/ecalc'd for C₂₀H₁₇N₃O₂: 331.1310, found: 331.1321.

Example LXII Preparation of3-(4-n-propylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using4′-n-propylacetophenone as the starting material. mp 269° C.; CIMS m/ecalc'd for C₂₁H₁₉N₃O₂: 346.1555, found: 346.1554.

Example LXIII Preparation of3-(4-methoxyphenyl)-5-carbamoylaminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII usingconcentrated ammonium hydroxide as the starting material. mp >300° C.;CIMS m/e calc'd for C₁₈H₁₅N₄O₃: 335.1144, found: 335.1113.

Example LXIV Preparation of3-(4-methoxyphenyl)-5-(dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII usingdimethylamino hydrazine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₀H₂₀N₅O₃: 378.1566, found: 378.1555.

Example LXV Preparation of3-(4-methoxyphenyl)-5-(methylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII usingmethylamine as the starting material. mp >300° C.; CIMS m/e calc'd forC₁₉H₁₇N₄O₃: 349.1300, found: 349.1311.

Example LXVI Preparation of3-(4-methoxyphenyl)-5-(morpholinocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII usingN-aminomorpholine as the starting material. mp >300° C.; CIMS m/e calc'dfor C₂₂H₂₂N₅O₄: 420.1671, found: 420.1655.

Example LXVII Preparation of3-(4-methoxyphenyl)-5-(cis-2-aminocyclohexanylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII usingcis-1,2-diaminocyclohexane as the starting material. mp >300° C.; CIMSm/e calc'd for C₂₄H₂₆N₅O₃: 432.2035, found: 432.2020.

Example LXVIII Preparation of3-(4-methoxyphenyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using(4-amino)methylpiperazine as the starting material. mp >300° C.; CIMSm/e calc'd for C₂₃H₂₅N₆O₃: 433.1987, found: 433.1999.

Example LXIX Preparation of3-(4-methoxyphenyl)-5-(4-uridomethylpiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingexample XXX as the starting material. mp >300° C.; CIMS m/e calc'd forC₂₆H₂₉N₆O₄: 489.2250, found: 489.2209.

Example LXX Preparation of3-(4-methoxyphenyl)-5-(4-(2-pyridyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-(2-pyridyl)piperazine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₈H₂₇N₆O₃: 495.2144, found: 495.2111.

Example LXXI Preparation of3-(4-methoxyphenyl)-5-(4-(aminoethyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-(aminoethyl)piperazine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₅H₂₉N₆O₃: 461.2300, found: 461.2333.

Example LXXII Preparation of3-(4-methoxyphenyl)-5-(4-amidopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingisonipecotamide as the starting material. mp >300° C.; CIMS m/e calc'dfor C₂₅H₂₆N₅O₄: 460.1984, found: 460.1998.

Example LXXIII Preparation of3-(4-methoxyphenyl)-5-(4-hydroxypiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-hydroxypiperadine as the starting material. mp >300° C.; CIMS m/ecalc'd for C₂₄H₂₅N₄O₄: 433.1875, found: 433.1844.

Example LXXIV Preparation of3-(4-methoxyphenyl)-5-(4-hydroxmethylypiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-hydroxmethylypiperadine as the starting material. mp >300° C.; CIMSm/e calc'd for C₂₅H₂₇N₄O₄: 447.2032, found: 447.2002.

Example LXXV Preparation of3-(4-methoxyphenyl)-5-(4-amidopiperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-amidopiperazine as the starting material. mp >300° C.; CIMS m/e calc'dfor C₂₄H₂₅N₆O₆: 493.1835, found: 493.1802.

Example LXXVI Preparation of3-(4-methoxyphenyl)-5-(4-dimethylaminopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-dimethylaminopiperadine as the starting material. mp >300° C.; CIMSm/e calc'd for C₂₆H₃₀N₅O₅: 492.2246, found: 492.2220.

Example LXXVII Preparation of3-(4-methoxyphenyl)-5-(4-aminopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-aminopiperadine as the starting material. mp >300° C.; CIMS m/e calc'dfor C₂₄H₂₆N₅O₅: 464.1933, found: 464.1975.

Example LXXVIII Preparation of3-(4-(dimethylamino)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LIV and 1-methylpiperazine as thestarting materials. mp >300° C.; ESI-MS m/e calc'd for C₂₅H₂₉N₆O₂:445.2352, found: 445.2359.

Example LXXIX Preparation of 3-(4-(dimethylamino)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LIV and 4-(aminomethyl)piperidine asthe starting materials. ESI-MS m/e calc'd for C₂₆H₃₁N₆O₂: 459.2508,found: 459.2508.

Example LXXX Preparation of3-(4-(dimethylamino)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LIV and 4-hydroxypiperidine as thestarting materials. mp 267° C.; ESI-MS m/e calc'd for C₂₅H₂₈N₅O₃:446.2192, found: 446.2206.

Example LXXXI Preparation of3-(4-(4-morpholinyl)phenyl)-5-(4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LVIII and morpholine as the startingmaterials. mp 258° C.; ESI-MS m/e calc'd for C₂₆H₂₈N₅O₄: 474.2141,found: 474.2151.

Example LXXXII Preparation of3-(4-(4-morpholinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LVIII and 1-methylpiperazine as thestarting materials. mp 258° C.; ESI-MS m/e calc'd for C₂₇H₃₁N₆O₃:487.2457, found: 487.2447.

Example LXXXIII Preparation of3-(4-(4-morpholinyl)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LVIII and 4-hydroxypiperidine as thestarting materials. mp 245° C.; ESI-MS m/e calc'd for C₂₇H₃₀N₅O₄:488.2298, found: 488.2290.

Example LXXXIV Preparation of 3-(4-(4-morpholinyl)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIIIemploying the product of example LVIII and 4-(aminomethyl)piperidine asthe starting materials. mp 240° C.; ESI-MS m/e calc'd for C₂₈H₃₃N₆O₃:501.2614, found: 501.2619.

Example LXXXV Preparation of3-(4-(dimethylamino)phenyl)-5-((((4-methyl-1-piperazinyl)amino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples I, XXVII, andXLII employing the 4-(dimethylamino) acetophenone and1-amino-4-methylpiperazine as the starting materials. mp >300° C.;ESI-MS m/e calc'd for C₂₄H₂₈N₇O₂: 446.2304, found: 446.2310.

Example LXXXVI Preparation of3-(i-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 26 from 3-nitrophthalic Anhydride.

A solution of 3-nitrophthalic anhydride (9.7 g, 50 mmol) and1,1,1-trifluoro-5-methyl-2,4-hexanedione (9.1 g, 50 mmol) in aceticanhydride (28.3 mL, 300 mmol) was treated with triethylamine (13.95 mL,100 mmol) and stirred at 25° C. for 4 h. The solution was diluted with 1N HCl (200 mL) and the precipate collected and washed with water (200mL) and hexane (400 mL) to give the product as a yellow solid (11.1 g,85%). mp 127-129° C.; CIMS (M+H) calc'd for C₁₃H₁₂NO₅: 262.0715, found:262.0694.

Step 2. Synthesis of triketone 27 from 26.

A solution of 26 (11 g, 42 mmol) in EtOH (224 mL) and water (56 mL) wastreated with zinc (90 g, 1.4 mol) and calcium chloride (3 g, 27 mmol)and heated to reflux for 16 h. The reaction was filtered (Celite) andthe filtrate was concentrated at reduced pressure to give an aqueousresidue which was extracted with EtOAc (100 mL). The organic layer wasseparated and washed with sat. EDTA (100 ml) and brine (100 mL), dried(MgSO₄), filtered, and concentrated at reduced pressure to give a yellowsolid. Trituration with hexane gave the product as a yellow solid (7.1g, 73%). mp 241-243° C.; CIMS (M+H) calc'd for C₁₃H₁₄NO₃: 232.0974,found: 232.0962.

Step 3. Synthesis of 28 from 27.

A solution of 27 (500 mg, 2.16 mmol) in CH2Cl2 (5 mL) was treated withEt3N (0.36 mL, 2.59 mmol) and stirred at 25° C. for 15 min. The reactionmixture was treated with acetyl chloride (0.18 mL, 2.38 mmol) andstirred at 25° C. for 1 h. The reaction mixture was quenched with 1 NHCl (20 mL) and extracted with EtOAc (20 mL). The organic layer wasseparated, dried (MgSO4), filtered, and concentrated at reduced pressureto give a brown residue. Trituration with hexane gave the product as atan solid (484 mg, 82%). mp 241-243° C.; CIMS (M+H) calc'd forC₁₅H₁₆NO₄: 274.1079, found: 274.1093.

Step 4. Synthesis of 29 from 28.

A solution of 28 (240 mg, 0.88 mmol) in BuOH (5 mL) was treated withhydrazine hydrate (0.055 mL, 1.76 mmol) and p-TsOH (8.4 mg, 0.044 mmol).The reaction was heated to reflux and stirred for 4 h. The reaction wascooled to 25° C. and the solvent removed at reduced pressure.Recrystalization with i-propyl alcohol gave the product collected as anoff-white solid (173 mg, 73%). mp >250° C.; ESIMS (M+H) calc'd forC₁₅H₁₆N₃O₂: 270.1242, found: 270.1258.

Example LXXXVII Preparation of3-(c-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using thec-propyl analog of 26 as the starting material. mp 220-221° C.; CIMS(M+H) calc'd for C₁₅H₁₄N₃O₂: 268.1086, found: 268.1078.

Example LXXXVIII Preparation of3-(t-butyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using thet-butyl analog of 26 as the starting material. mp >250° C.; CIMS (M+H)calc'd for C₁₆H₁₈N₃O₂: 284.1399, found: 284.1395.

Example LXXXIX Preparation of3-(2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the2-thienyl analog of 26 as the starting material. mp 269° C.; CIMS (M+H)calc'd for C₁₆H₁₂N₃O₂S: 310.0650, found: 310.0635.

Example XC Preparation of3-(3-methyl-2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the3-methyl-2-thienyl analog of 26 as the starting material. mp 275° C.;ESIMS (M+H) calc'd for C₁₇H₁₄N₃O₂S: 324.0811, found: 324.0807.

Example XCI Preparation of3-(ethyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the ethyl analog of 15 as the starting materials. mp >250°C.; CIMS (M+H) calc'd for C₁₃H₁₃N₄O₂: 257.1039, found: 257.1033.

Example XCII Preparation of3-(n-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the n-propyl analog of 15 as the starting materials. mp187-189° C.; CIMS (M+H) calc'd for C₁₄H₁₅N₄O₂: 271.1195, found:271.1187.

Example XCIII Preparation of3-(i-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the i-propyl analog of 15 as the starting materials.mp >250° C.; CIMS (M+H) calc'd for C₁₄H₁₅N₄O₂: 271.1195, found:271.1196.

Example XCIV Preparation of3-(c-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the c-propyl analog of 15 as the starting materials. mp252-253° C.; ESIMS (M-H) calc'd for C₁₄H₁₁N₄O₂: 267.0881, found:267.0884.

Example XCV Preparation of3-(c-hexyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the c-hexyl analog of 15 as the starting materials. mp178-179° C.; ESIMS (M+H) calc'd for C₁₇H₁₉N₄O₂: 311.1507, found:311.1500.

Example XCVI Preparation of3-(2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 2-thienyl analog of 15 as the starting materials. mp214° C.; CIMS m+ calc'd for C₁₅H₁₀N₄O₂S: 310.0517, found: 310.0524.

Example XCVII Preparation of3-(3-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 3-methyl-2-thienyl analog of 15 as the startingmaterials. mp 270° C.; ESIMS (M+H) calc'd for C₁₆H₁₃N₄O₂S: 325.0759,found: 325.0744.

Example XCVIII Preparation of3-(5-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 5-methyl-2-thienyl analog of 15 as the startingmaterials. mp >280° C.; ESIMS (M+H) calc'd for C₁₆H₁₃N₄O₂S: 325.0759,found: 325.0761.

Example XCIX Preparation of3-(5-ethylcarboxyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 5-ethylcarboxyl-2-thienyl analog of 15 as the startingmaterials. mp >280° C.; ESIMS (M+H) calc'd for C₁₈H₁₅N₄O₄S: 383.0813,found: 383.0788.

Example C Preparation of3-(3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 3-thienyl analog of 15 as the starting materials.mp >280° C.; ESIMS (M+H) calc'd for C₁₅H₁₁N₄O₂S: 311.0603, found:311.0594.

Example CI Preparation of3-(5-chloro-3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 5-chloro-3-thienyl analog of 15 as the startingmaterials. mp >300° C.; ESIMS (M+H) calc'd for C₁₅H₁₀N₄O₂SCl: 345.0209,found: 345.0213.

Example CII Preparation of3-(2,5-dimethyl-3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 2,5-dimethyl-3-thienyl analog of 15 as the startingmaterials. mp >280° C.; ESIMS (M+H) calc'd for C₁₇H₁₅N₄O₂S: 339.0916,found: 339.0905.

Example CIII Preparation of3-(2-furanyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 2-furanyl analog of 15 as the starting materials. mp278° C.; ESIMS (M+H) calc'd for C₁₅H₁₁N₄O₃: 295.0831, found: 295.0838.

Example CIV Preparation of3-(i-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the i-propyl analog of 15 as the startingmaterials. mp 231-233° C.; ESIMS (M+H) calc'd for C₁₆H₂₀N₅O₂: 314.1616,found: 314.1599.

Example CV Preparation of3-(c-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the c-propyl analog of 15 as the startingmaterials. mp XXX ° C.; ESIMS (M+H) calc'd for C₁₆H₁₈N₅O₂: 312.1460,found: 312.1487.

Example CVI Preparation of3-(c-hexyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the c-hexyl analog of 15 as the startingmaterials. mp 229-231° C.; ESIMS (M+H) calc'd for C₁₉H₂₄N₅O₂: 354.1929,found: 354.1932.

Example CVII Preparation of3-(2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the 2-thienyl analog of 15 as the startingmaterials. mp 279° C.; ESIMS (M+H) calc'd for C₁₇H₁₆N₅O₂S: 354.1024,found: 354.1025.

Example CVIII Preparation of3-(5-methoxy-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,l-dimethylhydrazine and the 5-methoxy-2-thienyl analog of 15 as thestarting materials. mp 280° C.; ESIMS (M+H) calc'd for C₁₈H₁₈N₅O₃S:384.1130, found: 384.1119.

Example CIX Preparation of3-(5-methyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the 5-methyl-2-thienyl analog of 15 as thestarting materials. mp >280° C.; ESIMS (M+H) calc'd for C₁₈H₁₈N₅O₂S:368.1181, found: 368.1171.

Example CX Preparation of3-(5-ethylcarboxyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using11-dimethylhydrazine and the 5-ethylcarboxyl-2-thienyl analog of 15 asthe starting materials. mp 252° C.; ESIMS (M+H) calc'd for C₂₀H₂₀N₅O₄S:426.1236, found: 426.1251.

Example CXI Preparation of3-(3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the 3-thienyl analog of 15 as the startingmaterials. mp 202° C.; ESIMS (M+H) calc'd for C₁₇H₁₆N₅O₂S: 354.1025,found: 354.1031.

Example CXII Preparation of3-(1-methyl-3-pyrrolyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI usingammonia and the 1-methyl-3-pyrrolyl analog of 15 as the startingmaterials. mp >300° C.; ESIMS (M+H) calc'd for C₁₆H₁₄N₅O₂: 308.1147,found: 308.1166.

Example CXIII Preparation of3-(2,5-dimethyl-3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the 2,5-dimethyl-3-thienyl analog of 15 as thestarting materials. mp 252° C.; ESIMS (M+H) calc'd for C₁₉H₂₀N₅O₂S:382.1338, found: 382.1357.

Example CXIV Preparation of3-(2-furanyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1,1-dimethylhydrazine and the 2-furanyl analog of 15 as the startingmaterials. mp 202° C.; ESIMS (M+H) calc'd for C₁₇H₁₆N₅O₃: 338.1253,found: 338.1248.

Example CXV Preparation of3-(i-propyl)-5-(4-carbamoylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingisonipecotamide and the i-propyl analog of 14 as the starting materials.mp 224-225° C.; ESIMS (M+H) calc'd for C₂₁H₂₆N₅O₃: 396.2035, found:396.2036.

Example CXVI Preparation of3-(c-hexyl)-5-(4-carbamoylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII usingisonipecotamide and the c-hexyl analog of 14 as the starting materials.mp 228-229° C.; ESIMS (M+H) calc'd for C₂₄H₃₀N₅O₃: 436.2348, found:436.2345.

Example CXVII Preparation of3-(ethyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-(aminomethyl)piperidine and the ethyl analog of 14 as the startingmaterials. mp 174-176° C.; ESIMS (M+H) calc'd for C₂₀H₂₆N₅O₂: 368.2086,found: 368.2078.

Example CXVIII Preparation of3-(i-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-(aminomethyl)piperidine and the i-propyl analog of 14 as the startingmaterials. mp 218-220° C.; ESIMS (M+H) calc'd for C₂₁H₂₈N₅O₂: 382.2242,found: 382.2227.

Example CXIX Preparation of3-(c-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-(aminomethyl)piperidine and the c-propyl analog of 14 as the startingmaterials. mp 138-140° C.; ESIMS (M+H) calc'd for C₂₁H₂₆N₅O₂: 380.2086,found: 380.2079.

Example CXX Preparation of3-(c-hexyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using4-(aminomethyl)piperidine and the c-hexyl analog of 14 as the startingmaterials. mp 196-198° C.; ESIMS (M+H) calc'd for C₂₄H₃₂N₅O₂: 422.2555,found: 422.2540.

Example CXXI Preparation of3-(i-propyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1-amino-4-methylpiperazine and the i-propyl analog of 15 as the startingmaterials. mp 231-233° C.; ESIMS (M+H) calc'd for C₁₉H₂₅N₆O₂: 369.2038,found: 369.2039.

Example CXXII Preparation of3-(5-ethylcarboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1-amino-4-methylpiperazine and the 5-ethylcarboxyl-2-thienyl analog of15 as the starting materials. mp 249° C.; ESIMS (M+H) calc'd forC₂₃H₂₅N₆O₄S: 481.1657, found: 481.1642.

Example CXXIII Preparation of3-(5-carboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

A solution of CXXII (30 mg, 0.05 mmol) in 3:1 THF/water (2 mL) wastreated with LiOH (23 mg, 0.5 mmol) and the reaction was stirred at 25°C. for 12 h and then heated to reflux for 1 h. The organic solvent wasremoved at reduced pressure and the residue was partioned between EtOAc(5 mL) and water (5 mL). The organic layer was separated and the aqueousphase was adjusted to pH=2 with 1 M HCl and re-extracted with EtOAc (5mL). The combined organic layers were dried (Na2SO4), filtered andconcentrated at reduced pressure to give a crude residue. Purificationby reverse phase HPLC gave the product as a yellow solid (10.4 mg, 46%).mp 270° C.; ESIMS (M+H) calc'd for C₂₁H₂₁N₆O₄S: 453.1344, found:453.1353.

Example CXXIV Preparation of3-(2,5-dimethyl-3-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using1-amino-4-methylpiperazine and the 2,5-dimethyl-3-thienyl analog of 15as the starting materials. mp 250° C.; ESIMS (M+H) calc'd forC₂₂H₂₅N₆O₂S: 437.1760, found: 437.1771.

Example CXXV Preparation of3-(i-propyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using4-aminomorpholine and the i-propyl analog of 15 as the startingmaterials. mp 256-258° C.; ESIMS (M−H) calc'd for C₁₈H₂₀N₅O₃: 354.1566,found: 354.1543.

Example CXXVI Preparation of3-(N-methylcarbamoyl-4-piperidinyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using4-aminomorpholine and the N-methylcarbamoyl-4-piperidinyl analog of 15as the starting materials. mp 216-218° C.; ESIMS (M+H) calc'd forC₂₂H₂₇N₆O₅: 455.2042, found: 455.2036.

Example CXXVII Preparation of3-(5-methyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using4-aminomorpholine and the 5-methyl-2-thienyl analog of 15 as thestarting materials. mp 261° C.; ESIMS (M+H) calc'd for C₂₀H₂₀N₅O₃S:410.1287, found: 410.1308.

Example CXXVIII Preparation of3-(5-chloro-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using4-aminomorpholine and the 5-chloro-3-thienyl analog of 15 as thestarting materials. mp 259° C.; ESIMS (M+H) calc'd for C₁₉H₁₇N₅O₃SCl:430.0741, found: 430.0757.

Example CXXIX Preparation of3-(2,5-dimethyl-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using4-aminomorpholine and the 2,5-dimethyl-3-thienyl analog of 15 as thestarting materials. mp >280° C.; ESIMS (M+H) calc'd for C₂₁H₂₂N₅O₃S:424.1443, found: 424.1431.

Example CXXX Preparation of3-(5-ethylcarboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using4-aminomorpholine and the 5-ethylcarboxyl-2-thienyl analog of 15 as thestarting materials. mp 258° C.; ESIMS (M+H) calc'd for C₂₂H₂₂N₅O₅S:468.1341, found: 468.1331.

Example CXXXI Preparation of3-(5-carboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI(HYDROLYSIS OF PREVIOUS ESTER). mp 273° C.; ESIMS (M+H) calc'd forC₂₀H₁₈N₅O₅S: 440.1028, found: 440.1026.

Example CXXXII Preparation of3-(5-benzylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

A solution of benzylamine (0.01 mL, 0.09 mmol) in DMF (1 mL) was treatedwith acid CXXXI (40 mg, 0.09 mmol) and stirred at 25° C. The reactionwas treated with TBTU (29 mg, 0.09 mmol) and stirred at 25° C. for 30min. Triethylamine (0.01 mL, 0.09 mmol) was added and the reactionstirred at 25° C. for 12 h. After adding more TBTU (15 mg, 0.045 mmol)and triethylamine (0.01 mL, 0.09 mmol) the reaction was stirred at 25°C. for an additional 4 h. The reaction was diluted with EtOAc (10 mL)and water (10 mL) and the aqueous layer was extracted with EtOAc (5×10mL). The combined organic layers were dried (Na2SO4), filtered, and thesolvent removed at reduced pressure. Purification of the residue usingreverse phase HPLC gave the product as a yellow solid (21 mg, 42%). mp275° C.; ESIMS (M+H) calc'd for C₂₇H₂₅N₅O₄S: 529.1659, found: 529.1682.

Example CXXXIII Preparation of3-(5-(4-methylpiperazinyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using1-amino-4-methylpiperazine as the starting material. mp 190° C.; ESIMS(M+H) calc'd for C₂₅H₂₉N₈O₄S: 537.2032, found: 537.2055.

Example CXXXIV Preparation of3-(5-(2-(1-methylpyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using2-(2-aminoethyl)-1-methylpyrrolidine as the starting material. mp 235°C.; ESIMS (M+H) calc'd for C₂₇H₃₂N₇O₄S: 550.2236, found: 550.2229.

Example CXXXV Preparation of3-(5-(N,N-dimethylamino)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using1,1-dimethylhydrazine as the starting material. mp 201° C.; ESIMS (M+H)calc'd for C₂₂H₂₄N₇O₄S: 482.1610, found: 482.1588.

Example CXXXVI Preparation of3-(5-(2-(N,N-dimethylamino)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII usingN,N-dimethylethylenediamine as the starting material. mp 190° C.; ESIMS(M+H) calc'd for C₂₄H₂₈N₇O₄S: 510.1923, found: 510.1922.

Example CXXXVII Preparation of3-(5-(2-(pyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using1-(2-aminoethyl)pyrrolidine as the starting material. mp 224° C.; ESIMS(M+H) calc'd for C₂₆H₃₀N₇O₄S: 536.2080, found: 536.2091.

Example CXXXVIII Preparation of3-(5-(2-(morpholinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using4-(2-aminoethyl)morpholine as the starting material. mp 241° C.; ESIMS(M+H) calc'd for C₂₆H₃₀N₇O₅S: 552.2029, found: 552.2043.

Example CXXXIX Preparation of3-(5-morpholinylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using4-aminomorpholine as the starting material. mp 271° C.; ESIMS (M+H)calc'd for C₂₄H₂₆N₇O₅S: 524.1716, found: 524.1719.

Example CXL Preparation of3-(5-(3-(pyrrolidonyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using1-(3-aminopropyl)-2-pyrrolidinone as the starting material. mp 260° C.;ESIMS (M+H) calc'd for C₂₇H₃₀N₇O₅S: 564.2029, found: 564.2031.

Example CXLI Preparation of3-(5-(2-(3-pyridyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using3-(2-aminoethyl)pyridine as the starting material. mp 203° C.; ESIMS(M+H) calc'd for C₂₇H₂₆N₇O₄S: 544.1766, found: 544.1760.

Example CXLII Preparation of3-(5-(3-(imidazolyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using1-(3-aminopropyl)imidazole as the starting material. mp 263° C.; ESIMS(M+H) calc'd for C₂₆H₂₇N₈O₄S: 547.1875, found: 547.1872.

Example CXLIII Preparation of3-(5-(2-(2-pyridyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using2-(2-aminoethyl)pyridine as the starting material. mp >280° C.; ESIMS(M+H) calc'd for C₂₇H₂₆N₇O₄S: 544.1767, found: 544.1778.

Example CXLIV Preparation of3-(5-((2-pyridyl)methyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using2-(aminomethyl)pyridine as the starting material. mp 239° C.; ESIMS(M+H) calc'd for C₂₆H₂₄N₇O₄S: 530.1610, found: 530.1603.

Example CXLV Preparation of3-(5-(2-(piperidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using1-(2-aminoethyl)piperidine as the starting material. mp 228° C.; ESIMS(M+H) calc'd for C₂₇H₃₂N₇O₄S: 550.2236, found: 550.2236.

Example CXLVI Preparation of3-(4-(trifluoromethyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI employing1-(4-(trifluoromethyl)phenyl)-4,4,4-trifluoro-1,3-butanedione as thestarting material. mp >300° C.; ESI⁻-MS m/e calc'd for C₁₉H₁₁N₃O₂:370.0804, found: 370.0809.

Example CXLVII Preparation of3-(4-(4-t-butoxycarbonyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 30.

A solution of 4-piperazinoacetophenone (24.8 g, 121 mmol) anddi-tert-butyl dicarbonate (27.8 g, 128 mmol) in 480 mL oftetrahydrofuran was refluxed for 16 h. After cooling to room temperaturethe solution was concentrated under vacuum. The resulting solids werewashed with hexane and dried under vacuum to afford 29.4 g (80%) of theproduct as an off-white solid. NMR (CDCl₃) δ7.89 (d, 2 H, J=9 Hz), 6.87(d, 2 H, J=9 Hz), 3.59 (m, 4 H), 3.33 (m, 4 H), 2.53 (s, 3 H), 1.49 (s,9 H).

Step 2. Synthesis of 31 from 30.

To a solution of 30 (11.35 g, 37 mmol) and ethyl trifluoroacetate (5.40mL, 45 mmol) in 50 mL of tetrahydrofuran at 25° C. was added dropwiseover 15 min. 21% sodium ethoxide in ethanol (16.8 mL, 45 mmol), and theresulting solution then was stirred at 25° C. for 14 h. The reactionmixture was diluted with water, adjusted to pH 5 with conc. hydrochloricacid, and extracted with ethyl acetate. The combined extracts was washedwith water and brine, dried over anhydrous sodium sulfate, filtered, andconcentrated under vacuum. The resulting solid was washed with diethylether and dried to furnish 12.1 g (81%) of the product as an orangesolid. NMR (CDCl₃) δ7.87 (d, 2 H, J=9 Hz), 6.87 (d, 2 H, J=9 Hz), 6.45(s, 1 H), 3.60 (m, 4 H), 3.41 (m, 4 H), 1.48 (s, 9 H).

Step 3. Synthesis of CXLVII from 31.

Prepared in a similar fashion as described for examples LXXVI and XLIIemploying 31 and 4-aminomorpholine as starting materials. mp 242° C.;ESI-MS m/e calc'd for C₃₀H₃₆N₇O₅574.2778, found: 574.2762.

Example CXLVIII Preparation of3-(4-(1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

A solution of CXLVII (0.58 g, 1.0 mmol) in 20 mL of trifluoroacetic acidwas stirred at 25° C. for 2 h. The reaction mixture was concentratedunder vacuum, and the residue was recrystallized from ethanol to provide0.53 g (89%) of the yellow product as its TFA-salt. mp 263° C.; ESI-MSm/e calc'd for C₂₅H₂₈N₇O₃: 474.2254, found: 474.2280.

Example CXLIX Preparation of3-(4-(1-piperazinyl)phenyl)-5-((aminocarbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples XLII and CXLVIIIemploying2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedioneobtained in example CXLVII and ammonia as the starting materials. mp257° C.; ESI-MS m/e calc'd for C₂₁H₂₁N₆O₂: 389.1726, found: 389.1724.

Example CL Preparation of3-(4-(1-piperazinyl)phenyl)-5-((hydrazinocarbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples XLII and CXLVIIIemploying2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedioneobtained in example CXLVII and hydrazine as the starting materials. mp257° C.; ESI-MS m/e calc'd for C₂₁H₂₂N₇O₂: 404.1835, found: 404.1834.

Example CLI Preparation of3-(4-(1-piperazinyl)phenyl)-5-((dimethylamino)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedioneobtained in example CXLVII as the starting material. Chloroacetylationand treatment with dimethylamine in a similar fashion as described forexamples II and XXIII, followed by treatment with hydrazine and removalof the t-butoxycarbonyl group in a similar fashion as described forexamples I and CXLVIII, afforded the example compound. mp 243° C.;ESI-MS m/e calc'd for C₂₄H₂₇N₆O₂: 431.2196, found: 431.2198.

Example CLII Preparation of3-(4-(1-piperazinyl)phenyl)-5-((4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedioneobtained in example CXLVII as the starting material. Chloroacetylationand treatment with morpholine in a similar fashion as described forexamples II and XXIII, followed by treatment with hydrazine and removalof the t-butoxycarbonyl group in a similar fashion as described forexamples I and CXLVIII, afforded the example compound. mp 259° C.;ESI-MS m/e calc'd for C₂₆H₂₉N₆O₃: 473.2301, found: 473.2302.

Example CLIII Preparation of3-(4-(1-piperazinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedioneobtained in example CXLVII as the starting material. Chloroacetylationand treatment with 1-methylpiperazine in a similar fashion as describedfor examples II and XXIII, followed by treatment with hydrazine andremoval of the t-butoxycarbonyl group in a similar fashion as describedfor examples I and CXLVIII, afforded the example compound. ESI-MS m/ecalc'd for C₂₇H₃₂N₇O₂: 486.2618, found: 486.2608.

Example CLIV Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedioneobtained in example CXLVII as the starting material. Chloroacetylationand treatment with 4-(aminomethyl)piperidine in a similar fashion asdescribed for examples II and XXIII, followed by treatment withhydrazine and removal of the t-butoxycarbonyl group in a similar fashionas described for examples I and CXLVIII, afforded the example compound.mp 239° C.; ESI-MS m/e calc'd for C₂₈H₃₄N₇O₂: 500.2774, found: 500.2772.

Example CLV Preparation of3-(4-(4-methyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

To a solution of CXLVIII (0.17 g, 0.29 mmol) in 10 mL of methanol and 2mL of water at 25° C. was added sequentially 37% aqueous formaldehyde(0.45 g, 5.8 mmol), sodium cyanoborohydride (0.18 g, 2.9 mmol), and 4drops of acetic acid. The resulting solution was stirred at 25° C. for16 h. The mixture was diluted with water. It then was made acidic(˜pH 1) with conc. hydrochloric acid and stirred for 10 min. Thesolution next was made basic (˜pH 13) with 50% aqueous sodium hydroxideand finally adjusted to pH 10 with 1 N hydrochloric acid. The mixturewas extracted with 4:1 chloroform/isopropanol. The combined extractswere washed with water and brine, dried over anhydrous sodium sulfate,and filtered. To the filtrate was added excess trifluoroacetic acid, andthe solution was concentrated under vacuum. The residue wasrecrystallized from isopropanol to furnish 0.16 g (92%) of the yellowproduct as its TFA-salt. mp 245° C.; ESI-MS m/e calc'd for C₂₆H₃₀N₇O₃:488.2410, found: 488.2420.

Example CLVI Preparation of3-(4-(4-ethyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLV employingCXLVIII and acetaldehyde as the starting materials. mp 245° C.; ESI-MSm/e calc'd for C₂₇H₃₂N₇O₃: 502.2567, found: 502.2555.

Example CLVII Preparation of3-(4-(4-isopropyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLV employingCXLVIII and acetone as the starting materials. mp 253° C.; ESI-MS m/ecalc'd for C₂₈H₃₄N₇O₃: 516.2723, found: 516.2726.

Example CLVIII Preparation of3-(4-methoxyphenyl)-5-(2-benzoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 31 from 13.

A suspension of aniline 31 (0.5 g, 1.7 mmol) in dioxane (10 mL) wastreated with triethylamine (0.48 mL, 3.4 mmol) in one portion at roomtemperature. Then 2-(trimethylsilyl) ethyloxy chloride (SEMCl) (0.48 mL,2.6 mmol) was added in one portion and the mixture heated to reflux for2 h. The reaction was cooled, diluted with EtOAc (20 mL) washed withwater (10 mL), dried (MgSO4) and the solvent removed at reducedpressure. The residue was taken up in benzene (3 mL), applied to a plugof silica gel (10 g) and eluted with EtOAc/Hexane (1:3) until all theyellow color was washed from the silica gel plug. The solvent wasevaporated and the residue taken on to the next step. This material wasdissolved in dioxane (10 mL) and treated with K2CO3 (0.36 g, 2.6 mmol)in one portion. Then phenylchloroformate (0.27 mL, 2.23 mmol) was addedin one portion and the reaction heated to 50 C. for 2 h. The reactionwas cooled and the solvent removed at reduced pressure. The residue wasrecrystalized from EtOH to give a yellow solid (0.4 g, 43%). mp °C.;CIMS m/e calculated for C₃₀H₃₂N₃O₅Si: 542.2111, found: 542.2101;

Step 2. Synthesis of Ex. CLVIII from 31.

Compound 31 (0.015 g, 0.03 mmol) in DMSO (0.2 mL) was treated withphenylcarbazte (0.008 g, 0.06 mmol) in one portion and heated to 80 C.for 30 minutes. The solvent was removed at reduced pressure heating to65 C. The residue was disolved in EtOH (0.5 mL) and treated with 4NHCl/dioxane (0.4 mL). The mixture was heated to 80 C. for 20 minutes andthen cooled. The desired product was filtered and air dried (0.008 g,62%). mp >300° C.; CIMS m/e calculated for C₂₆H₂₇N₄O₄: 459.2032, found:459.1999;

Example CLIX Preparation of3-(4-methoxyphenyl)-5-(2-isonicotinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using4-pyridylcarbazate as the starting material. mp 248° C.; CIMS m/ecalculated for C₂₄H₁₉N₆O₄: 455.1468, found: 455.1400;

Example CLX Preparation of3-(4-methoxyphenyl)-5-(2-nictinoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using3-pyridylcarbazate as the starting material. mp 227° C.; CIMS m/e calc'dfor C₂₄H₁₉N₆O₄: 455.1468, found: 455.1487;

Example CLXI Preparation of 3-(4-methoxyphenyl)-5-(2-(3,4-dihydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using3,4-dihydroxyphenyl carbazate as the starting material. mp >300° C.;CIMS m/e calc'd for C₂₅H₂₀N₅O₆: 486.1414, found: 486.1497;

Example CLXII Preparation of 3-(4-methoxyphenyl)-5-(2-(4-hydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using4-hydroxyphenyl carbazate as the starting material. mp 283° C.; CIMS m/ecalc'd for C₂₅H₂₀N₅O₅: 470.1464, found: 470.1544;

Example CLXIII Preparation of3-(4-methoxyphenyl)-5-(2-(3-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using3-aminophenyl carbazate as the starting material. mp 250° C.; CIMS m/ecalc'd for C₂₅H₂₁N₆O₄: 469.1624, found: 469.1513;

Example CLXIV Preparation of3-(4-methoxyphenyl)-5-(2-(4-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using4-aminophenyl carbazate as the starting material. mp 247° C.; CIMS m/ecalc'd for C₂₅H₂₁N₆O₄: 469.1624, found: 469.1528;

Example CLXV Preparation of3-(4-methoxyphenyl)-5-(2-(2-aminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using2-aminophenyl carbazate as the starting material. mp 257° C.; CIMS m/ecalc'd for C₂₅H₂₁N₆O₄: 469.1624, found: 469.1548;

Example CLXVI Preparation of3-(4-methoxyphenyl)-5-(2-(4-N,N-dimethylaminobenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using4-N,N-dimethylaminophenyl carbazate as the starting material. mp 259°C.; CIMS m/e calc'd for C₂₇H₂₅N₆O₄: 497.1937, found: 497.1876;

Example CLXVII Preparation of 3-(4-methoxyphenyl)-5-(2-phenethylacetylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII usingbenzyl carbazate as the starting material. mp 269° C.; CIMS m/e calc'dfor C₂₆H₂₂N₅O₄: 468.1672, found: 468.1313;

Example CLXVIII Preparation of3-(4-methoxyphenyl)-5-(2-(2-hydroxybenzoyl)hydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII using2-hydroxyphenyl carbazate as the starting material. mp 280° C.; CIMS m/ecalc'd for C₂₅H₂₀N₅O₅: 470.1464, found: 470.1419;

Example CLXIX Preparation of3-(4-methoxyphenyl)-5-(2-methoxycarbonylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLVIII usingcarbazic acid methyl ester as the starting material. mp >300° C.; CIMSm/e calc'd for C₂₀H₂₈N₅O₅: 408.1308, found: 408.1397;

EXAMPLE CLXX Preparation of Intermediate CLXX

The preparation of intermediate CLXX,(N-[2-(4-Methoxy-benzoyl)-1,3-dioxo-indan-4-yl]-acetamide) is describedin Nugiel, D. A.; Etzkorn, A. M.; Vidwans, A.; Benfield, P. A.;Boisclair, M.; Burton, C. R.; Cox, S.; Czerniak, P. M.; Doleniak, D.;Seitz, S. P. J. Med. Chem. 2001, 44, 1334-1336 which is hereinincorporated by reference in it's entirety as though set forth in full.

EXAMPLE CLXXI Preparation of Intermediate CLXXI

Synthesis of 4-Amino-2-(4-methoxy-benzoyl)-indan-1,3-dione: The compoundprepared in example 1 (2.0 g, 5.93 mmol) is dissolved in 20% HCl inmethanol (50 mL). This solution is stirred at reflux for a period of 3h. It is then allowed to cool to room temperature and stirred overnight.The product is filtered off, washed with ethanol (20 mL) and air driedto give the product as a yellow solid (1.5 g, 85.7%). mp 268-269° C.; ¹HNMR (DMSOd₆) δ8.17 (d, J=8.8 Hz, 2H), 7.49 (t, 1H), 7.12 (d, J=8.7 Hz,2H), 6.98 (m, 2H), 3.88 (s, 1H).

EXAMPLE CLXXII Preparation of Intermediate CLXXII

Synthesis of [2-(4-Methoxybenzoyl)-1,3-dioxo-indan-4-yl]-carbamic acidphenyl ester: The product prepared in Example CLXXI (1.5 g, 5.08 mmol)is dissolved in acetone (40 mL) and treated with sodium carbonate (1.26g, 15.24 mmol) and phenyl chloroformate (1.19 g, 7.62 mmol). Thesuspension is stirred at 50° C. for 3 h. The reaction mixture is dilutedwith water (120 mL), and extracted with ethyl acetate (2×100 mL). Theorganic layer is separated, washed with brine (50 mL), dried (Na₂SO₄)and the solvent removed at reduced pressure to give a gummy orangeresidue. Cold ethyl ether (100 mL) is added to this residue to give aprecipitate. The precipitate is collected and washed with ethyl ether(2×10 mL) to give desired product as a yellow solid (1.65 g. 78%). mp256-258° C.; ¹H NMR (DMSOd₆) δ10.83 (s, 1H), 8.08 (d, J=8.0 Hz, 1H),7.57 (d, J=2.9 Hz, 2H), 7.54 (m, 3H), 7.28 (m, 3H), 7.09 (t, 1H), 6.89(d, J=10.8 Hz, 2H), 3.81 (s, 3H).

EXAMPLE CLXXIII Preparation of1-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-yl-urea

The product prepared in Example CLXXII (0.03 g, 0.072 mmol) in anhydrousDMSO (2 mL) is treated with 4-aminomorpholine (0.0084 g, 0.082 mmol) and4-dimethylaminopyridine (0.005 g, 0.04 mmol) and heated to 80° C. for 3h. The solvent is removed under reduced pressure and the residuetriturated with ethanol to give a dark solid. The solid is collected andwashed with ethanol (5 mL) to give a tricarbonyl urea (0.03 g, 100%).The tricarbonyl urea intermediate (0.03 g, 0.078 mmol) is treated withhydrazine hydrate (0.1 mL, 3.21 mmol) and p-toluenesulfonic acidmonohydrate (0.01 g, 0.05 mmol) in refluxing ethanol (4 mL) for a periodof 3 h. The reaction mixture is cooled to room temperature, the solidcollected, washed with cold ethanol (2×2 mL), and air dried to give theproduct as a yellowish solid (0.012 g, 41.3%). mp 290-291° C.; ¹H NMR(DMSO-d₆) δ8.27 (d, J=6.8 Hz, 2H), 8.16 (d, J=8.8 Hz, 2H), 7.42 (m, 1H),7.12 (m, 3H), 3.81 (s, 3H), 2.90 (s, 4H), 2.70 (s, 4H), HRMS calcd. forC₂₂H₂₂N₅O₄ (M+H⁺) 420.1672; found 420.1688;

EXAMPLE CLXXIV Preparation of[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea

The product prepared in Example CLXXII (0.03 g, 0.072 mmol) in anhydrousDMSO (2 mL) is treated with excess ammonium hydroxide solution and4-dimethylaminopyridine (0.005 g, 0.04 mmol) and is heated to 80° C. for3 h. The solvent is removed under reduced pressure and the residuetriturated with ethanol to give a dark solid. The solid is collected andwashed with ethanol (5 mL) to give urea (0.03 g, 100%). The tricarbonylurea intermediate (0.03 g, 0.078 mmol) is treated with hydrazine hydrate(0.1 mL, 3.21 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.05mmol) in refluxing ethanol (4 mL) for a period of 3 h. The reactionmixture is cooled to room temperature, the solid collected, washed withcold ethanol (2×2 mL), and air dried to give the product as a yellowishsolid (0.018 g, 62.4%). mp 267-269° C.; ¹H NMR (DMSO-d₆) δ9.35 (s, 1H),8.22 (m, 3H), 7.38 (m, 1H), 7.10 (d, J=8.8 Hz, 2H), 7.02 (d, J=7 Hz,1H), 3.81 (s, 3H); HRMS calcd. for C₁₈H₁₅N₄O₃ (M+H⁺) 335.1144; found335.1162;

EXAMPLE CLXXV Preparation of1-(2-amino-cyclohexyl)-3-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-urea

The product prepared in Example CLXXII (0.03 g, 0.072 mmol) in anhydrousDMSO (2 mL) is treated with 1,2-diaminocyclohexane (0.01 g, 0.082 mmol)and 4-dimethylaminopyridine (0.005 g, 0.04 mmol) and heated to 80° C.for 3 h. The solvent is removed under reduced pressure and the residuetriturated with ethanol to give a dark solid. The solid is collected andwashed with ethanol (5 mL) to give a tricarbonyl urea (0.03 g, 100%).The tricarbonyl urea intermediate (0.03 g, 0.078 mmol) is treated withhydrazine hydrate (0.1 mL, 3.21 mmol) and p-toluenesulfonic acidmonohydrate (0.01 g, 0.05 mmol) in refluxing ethanol (4 mL) for a periodof 3 h. The reaction mixture is cooled to room temperature, the solidcollected, washed with cold ethanol (2×2 mL), and air dried to give theproduct as a yellowish solid (0.01 g, 30.6%). ¹HNMR (DMSO-d₆) δ9.56 (s,1H), 8.27 (d, 1H), 8.19 (d, 2H), 7.41 (t, 1H), 7.10 (m, 3H), 4.10 (s,1H), 3.81 (s, 3H), 3.23 (s, 1H), 1.63 (m, 5H), 1.40 (m, 3H).

EXAMPLE CLXXVI Preparation of5-Amino-3-(4-methoxyphenyl)-2-phenyl-2H-indeno-[1,2-c]pyrazol-4-one:

A suspension ofN-[3-(4-Methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide(as produced according to Nugiel, D. A.; Etzkorn, A. M.; Vidwans, A.;Benfield, P. A.; Boisclair, M.; Burton, C. R.; Cox, S.; Czerniak, P. M.;Doleniak, D.; Seitz, S. P. J. Med. Chem. 2001, 44, 1334-1336) (1.0 g,3.0 mmol) in MeOH (10 mL) was treated with concentrated HCl (1 mL) andheated to reflux. After stirring the mixture for 2 h the reaction wascooled and the product was collected by filtration and obtained as agreenish solid (0.7 g, 81%). mp 273° C.; NMR (DMSO-d₆) δ13.6 (bs, 1 H),8.3 (d, J=8.4 Hz, 1 H), 8.1 (d, J=8.8 Hz, 2 H), 7.5 (t, J=7.7 Hz 1 H),7.2 (d, J=7.0 Hz, 1 H), 7.1 (d, J=8.8 Hz, 2 H), 3.8 (s, 3 H); HRMS m/ecalc'd for C₁₇H₁₄N₃O₂ (M+H): 292.1086, found: 292.1080.

EXAMPLE CLXXVII Preparation of2-Chloro-N-[3-(4-methoxyphenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide

A suspension of the product prepared in Example CLXXVI (0.2 g, 0.7 mmol)in dioxane (10 mL) was treated with aqueous saturated NaHCO₃ (3 mL) andchloroacetyl chloride (3 mL, 0.21 mmol). The reaction was heated to 50°C. and stirred for 2 h. The reaction is then cooled, poured into water(20 mL), extracted with EtOAc (100 mL), the organic layer separated,dried (MgSO₄) and the solvent removed at reduced pressure. The residueis recrystallized from EtOH to give the product as a yellow solid (0.09g, 35%). mp >300° C.; NMR (DMSO-d₆) δ13.6 (bs, 1 H), 11.3 (s, 1 H), 8.3(d, J=8.4 Hz, 1 H), 8.1 (d, J=8.8 Hz, 2 H), 7.5 (t, J=7.7 Hz 1 H), 7.2(d, J=7.0 Hz, 1 H), 7.1 (d, J=8.8 Hz, 2 H), 4.5 (s, 2 H), 3.8 (s, 3 H);HRMS m/e calc'd for C₁₉H₁₅N₃O₃Cl (M+H): 368.0802, found: 368.0818.

EXAMPLE CLXXVIII Preparation of2-(4-aminomethyl-piperidin-1-yl)-N-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-acetamide

A suspension of product prepared according to Example CLXXVII (0.015 g,0.04 mmol) in EtOH (1 mL) is treated with 4-aminomethylpiperdine (0.75mL), placed in a sealed tube and heated to 80° C. for 3 h. The reactionis cooled and the solvent removed at reduced pressure. The residue isrecrystallized from EtOH to give the product as a yellow solid (0.009 g,62%). mp >300° C.; NMR (DMSO-d₆) δ13.6 (bs, 1 H), 11.3 (s, 1 H), 8.35(d, J=8.4 Hz, 1 H), 8.1 (d, J=8.8 Hz, 2 H), 7.5 (t, J=7.7 Hz 1 H), 7.2(d, J=7.0 Hz, 1 H), 7.1 (d, J=8.8 Hz, 2 H), 3.8 (s, 3 H), 3.2 (bs, 2 H),2.9(bs, 2 H), 2.5 (d, J=8.0 Hz, 2 H), 2.2 (t, J=8.0 Hz, 2 H), 1.6 (m, 5H); HRMS m/e calc'd for C₂₅H₂₈N₅O₃ (M+H): 446.2192, found: 446.2169;Anal. (C₂₅H₂₇N₅O₃) C, H, N.

EXAMPLE CLXXIX Preparation of2-(4-Methoxybenzoyl)-3-methoxycarbonylamino-indan-1,3-dione

A solution of 3-methoxycarbonylamino-phthalic acid dimethyl ester (1 g,4.8 mmol) and 4-methoxyacetophenone (0.72 g, 4.8 mmol) in dry DMF (3 mL)was heated to 90° C. Sodium hydride (0.21 g, 60% suspension in oil, 5.2mmol) is added in one portion and the exothermic reaction turns deepred. After 20 min, the reaction is cooled to room temperature, dilutedwith water (25 mL) extracted with EtOAc (10 mL) and the aqueous phaseseparated. The aqueous phase is acidified to pH 2 with 2N HCl and thecrude product collected. Recrystallization with ethanol gives thedesired product as a yellow solid (0.4 g, 30%). ESIMS 352 (M−H, 100%).

EXAMPLE CLXXX Preparation of3-(4-Methoxyphenyl)-5-methoxycarbonylamino-2H-indeno-[1,2-c]pyrazol-4-one

A solution of2-(4-methoxybenzoyl)-3-methoxycarbonylamino-indan-1,3-dione (0.2 g, 0.6mmol) in EtOH (5 mL) is treated with hydrazine hydrate (0.1 mL, 1.8mmol) and p-TsOH (3 mg). The reaction is heated to reflux and stirredfor 2 h. The reaction is cooled to room temperature and the productcrystallized from the reaction mixture. The product is collected byfiltration as a yellow solid (0.1 g, 50%). mp >300° C.; HRMS m/e calc'dfor C₁₉H₁₆N₃O₄ (M+H): 350.1141, found: 350.1168.

Utility Inhibition of Kinase/Cyclin Complex Enzymatic Activity

Several of the compounds disclosed in this invention were assayed fortheir inhibitory activity against cdk4/D1 and cdk2/E kinase complexes.Briefly, the in vitro assays employ cell lysates from insect cellsexpressing either of the kinases and subsequently their correspondingregulatory units. The cdk2/cyclinE is purified from insect cellsexpressing His-tagged cdk2 and cyclin E. The cdk/cyclin lysate iscombined in a microtitre-type plate along with a kinase compatiblebuffer, ³²P-labeled ATP at a concentration of 50 mM, a GST-Rb fusionprotein and the test compound at varying concentrations. The kinasereaction is allowed to proceeded with the radiolabled ATP, theneffectively stopped by the addition of a large excess of EDTA andunlabeled ATP. The GST-Rb labeled protein is sequestered on aGSH-Sepharose bead suspension, washed, resuspended in scintillant, andthe ³²P activity detected in a scintillation counter. The compoundconcentration which inhibits 50% of the kinase activity was calculatedfor each compound. A compound was considered active if its IC₅₀ wasfound to be less than 1 μM.

Inhibition of HCT 116 Cancer Cell Proliferation

To test the cellular activity of several compounds disclosed in thisinvention, we examined the effect of these compounds on cultured HCT116cells and determined their effect on cell-cycle progression by thecalorimetric cytotoxcity test using sulforhodamine B (Skehan et al. J.Natl. Cancer Inst. 82:1107-12, 1990). Briefly, HCT116 cells are culturedin the presence of test compounds at increasing concentrations. Atselected time points, groups of cells are fixed with trichloroaceticacid and stained with sulforhodamine B (SRB). Unbound dye was removed bywashing and protein-bound dye was extracted for determination of opticaldensity. A compound was considered active if its IC₅₀ was found to beless than 10 μM.

TABLE 1

Example mass mp # R¹ R² (M⁺H) (° C.) I Methyl 4-MeOC₆H₄ 334 268 II ClCH₂4-MeOC₆H₄ 382 274 III Cyclopropyl 4-MeOC₆H₄ 360 289 IV Isopropyl4-MeOC₆H₄ 362 288 V Ethyl 4-MeOC₆H₄ 348 287 VI Cyclopentyl 4-MeOC₆H₄ 388267 VII Cyclobutyl 4-MeOC₆H₄ 374 297 VIII Benzyl 4-MeOC₆H₄ 410 280 IXn-propyl 4-MeOC₆H₄ 362 282 X 4-ClC₆H₄CH₂ 4-MeOC₆H₄ 444 238 XI3-MeOC₆H₄CH₂ 4-MeOC₆H₄ 440 >300 XII 4-MeOC₆H₄CH₂ 4-MeOC₆H₄ 440 280 XIII3,4-diMeOC₆H₄CH₂ 4-MeOC₆H₄ 470 >300 XIV 2,5-diMeOC₆H₄CH₂ 4-MeOC₆H₄ 470226 XV Methyl 2-MeOC₆H₄ 334 276 XVI Methyl 3,4-diMeOC₆H₄ 364 >300 XVII3,4-(OCH₂O)C₆H₄CH₂ 4-MeOC₆H₄ 454 297 XVIII 3-thiophenylCH₂ 4-MeOC₆H₄ 416293 XIX 2-MeOC₆H₄CH₂ 4-MeOC₆H₄ 440 255 XX 3,4-diClOC₆H₄CH₂ 4-MeOC₆H₄ 479299 XXI 2,4-diClOC₆H₄CH₂ 4-MeOC₆H₄ 479 286 XXII 2-ClC₆H₄CH₂ 4-MeOC₆H₄444 300 XXIII H₂NCH₂ 4-MeOC₆H₄ 349 >300 XXIV HOCH₂CH₂NHCH₂ 4-MeOC₆H₄ 393243 XXV Me₂NCH₂ 4-MeOC₆H₄ 377 279 XXVI piperazinylCH₂ 4-MeOC₆H₄ 418 277XXVII 4-Me-piperazinylCH₂ 4-MeOC₆H₄ 432 >300 XXVIII 4-HOCH₂CH₂-4-MeOC₆H₄ 462 >300 piperazinylCH₂ XXIX piperidinylCH₂ 4-MeOC₆H₄ 417 291XXX 4-NH₂CH₂- 4-MeOC₆H₄ 446 >300 piperidinylCH₂ XXXI CH₃CH₂NHCH₂4-MeOC₆H₄ 377 250 XXXII ThiomorpholinylCH₂ 4-MeOC₆H₄ 435 298 XXXIIImorpholinylCH₂ 4-MeOC₆H₄ 419 295 XXXIV pyrrolidinylCH₂ 4-MeOC₆H₄ 403 279XXXV 4-pyridylCH₂NHCH₂ 4-MeOC₆H₄ 440 >300 XXXVI 4-CH₃CONHC₆H₄CH₂4-MeOC₆H₄ 467 268 XXXVII 4-CH₃OCONHC₆H₄CH₂ 4-MeOC₆H₄ 483 257 XXXVIII4-NH₂CH₂CONHC₆H₄CH₂ 4-MeOC₆H₄ 482 228 XXXIX 4-Me₂NCH₂CONHC₆H₄CH₂4-MeOC₆H₄ 510 >300 XL 4-N₃C₆H₄CH₂ 4-MeOC₆H₄ 451 >300 XLI 4-NH₂C₆H₄CH₂4-MeOC₆H₄ 425 283 XLII C₆H₅NH 4-MeOC₆H₄ 411 >300 XLIII CH₃CH₂CH₂NH4-MeOC₆H₄ 377 252 XLIV 4-NH₂C₆H₄CH₂NH 4-MeOC₆H₄ 440 >300 XLV4-pyridylCH₂NH 4-MeOC₆H₄ 426 >300 XLVI Methyl 4-HOC₆H₄ 320 >300 XLVII H4-MeOC₆H₄ 320 280 XLVIII Methyl 3-pyridyl 305 >300 XLIX Methyl 4-pyridyl305 >300 L H 4-pyridyl 291 >300 LI Methyl C₆H₅ 305 >300 LII Methyl4-MeSC₆H₄ 351 283 LIII Methyl 4-MeSO₂C₆H₄ 383 >300 LVI Methyl 4-Me₂NC₆H₄348 >300 LV morpholinylCH₂ 4-Me₂NC₆H₄ 432 >300 LVI Me₂NCH₂ 4-Me₂NC₆H₄390 >300 LVII Methyl 4-(piperdinyl)C₆H₄ 388 291 LVIII Methyl4-(morpholinyl)C₆H₄ 389 >300 LIX Methyl 4-CH₃CH₂OC₆H₄ 349 288 LX Methyl4-CH₃CH₂CH₂CH₂C₆H₄ 361 259 LXI Methyl 4-CH₃CH₂C₆H₄ 332 294 LXII Methyl4-CH₃CH₂CH₂C₆H₄ 347 269 LXIII NH₂ 4-MeOC₆H₄ 335 >300 LXIV Me2NNH4-MeOC₆H₄ 378 >300 LXV MeNH 4-MeOC₆H₄ 349 >300 LXVI MorpholinylNH4-MeOC₆H₄ 420 >300 LXVII cis-1,2- 4-MeOC₆H₄ 432 >300 diaminocyclohexanylLXVIII 4-methyl- 4-MeOC₆H₄ 433 >300 piperazinylNH LXVIX 4-uridomethyl-4-MeOC₆H₄ 489 >300 piperadinylCH₂ LXX 4-(2-pyridyl)- 4-MeOC₆H₄ 495 >300piperazinyl CH₂ LXXI 4-(aminoethyl)- 4-MeOC₆H₄ 461 >300 piperazinyl CH₂LXXII 4-amidopiperidinylCH₂ 4-MeOC₆H₄ 460 >300 LXXIII 4-hydroxy-4-MeOC₆H₄ 433 >300 piperidinylCH₂ LXXIV 4-hydroxy- 4-MeOC₆H₄ 447 >300methylpiperidinylCH₂ LXXV 4-amidopiperazinylCH₂ 4-MeOC₆H₄ 493 >300 LXXVI4-dimethyl- 4-MeOC₆H₄ 492 >300 aminopiperadinylCH₂ LXXVII4-aminopiperadinylCH₂ 4-MeOC₆H₄ 464 >300 LXXVIII 4-Me-piperazinylCH₂4-Me₂NC₆H₄ 445 >300 LXXIX 4-NH₂CH₂- 4-Me₂NC₆H₄ 459 NA piperidinylCH₂LXXX 4-OH-piperidinylCH₂ 4-Me₂NC₆H₄ 446 267 LXXXI morpholinylCH₂4-(morpholinyl)C₆H₄ 474 258 LXXXII 4-Me-piperazinylCH₂4-(morpholinyl)C₆H₄ 487 258 LXXXIII 4-OH-piperidinylCH₂4-(morpholinyl)C₆H₄ 488 245 LXXXIV 4-NH₂CH₂- 4-(morpholinyl)C₆H₄ 501 240piperidinylCH₂ LXXXV 4-Me-piperazinylNH 4-Me₂NC₆H₄ 446 >300 LXXXVIMethyl i-propyl 270 >250 LXXXVII Methyl c-propyl 268 220 LXXXVIII Methylt-butyl 284 >250 LXXXIX Methyl 2-thienyl 310 269 XC Methyl3-Me-2-thienyl 324 275 XCI NH₂ Ethyl 257 >250 XCII NH₂ n-propyl 271 187XCIII NH₂ i-propyl 271 >250 XCIV NH₂ c-propyl 267 252 (M − H) XCV NH₂c-hexyl 311 178 XCVI NH₂ 2-thienyl 310 214 (M+) XCVII NH₂ 3-Me-2-thienyl325 270 XCVIII NH₂ 5-Me-2-thienyl 325 >280 XCIX NH₂ 5-CO₂Et-2-thienyl383 >280 C NH₂ 3-thienyl 311 >280 CI NH₂ 5-Cl-3-thienyl 345 >300 CII NH₂2,5-diMe-3-thienyl 339 >280 CIII NH₂ 2-furanyl 295 278 CIV Me₂NNHi-propyl 314 231 CV Me₂NNH c-propyl 312 CVI Me₂NNH c-hexyl 354 229 CVIIMe₂NNH 2-thienyl 354 279 CVIII Me₂NNH 5-MeO-2-thienyl 384 280 CIX Me₂NNH5-Me-2-thienyl 368 >280 CX Me₂NNH 5-CO₂Et-2-thienyl 426 252 CXI Me₂NNH3-thienyl 354 202 CXII NH₂ 1-methyl-3- 308 >300 pyrrolyl CXIII Me₂NNH2,5-diMe-3-thienyl 382 252 CXIV Me₂NNH 2-furanyl 338 202 CXV 4-NH₂CO-i-propyl 396 224 piperidinylCH₂ CXVI 4-NH₂CO- c-hexyl 436 228piperidinylCH₂ CXVII 4-NH₂CH₂- ethyl 368 174 piperidinylCH₂ CXVIII4-NH₂CH₂- 1-propyl 382 218 piperidinylCH₂ CXVIX 4-NH₂CH₂- c-propyl 380138 piperidinylCH₂ CXX 4-NH₂CH₂- c-hexyl 422 196 piperidinylCH₂ CXXI4-CH₃-piperazinylNH i-propyl 369 231 CXXII 4-CH₃-piperazinylNH5-CO₂Et-2-thienyl 481 249 CXXIII 4-CH₃-piperazinylNH 5-CO₂H-2-thienyl453 270 CXXIV 4-CH₃-piperazinylNH 2,5-diMe-3-thienyl 437 250 CXXVMorpholinylNH i-propyl 354 256 (M − H) CXXVI MorpholinylNH 4-CO₂Me- 455216 piperidinyl CXXVII MorpholinylNH 5-Me-2-thienyl 410 261 CXXVIIIMorpholinylNH 5-Cl-3-thienyl 430 259 CXXIX MorpholinylNH2,5-diMe-3-thienyl 424 >280 CXXX MorpholinylNH 5-CO₂Et-2-thienyl 468 258CXXXI MorpholinylNH 5-CO₂H-2-thienyl 440 273 CXXXII MorpholinylNH5-CONHBn-2-thienyl 529 275 CXXXIII MorpholinylNH 5-CONH(4-Me- 537 190piperazinyl)-2- thienyl CXXXIV MorpholinylNH 5-CONHCH₂CH₂(1-Me- 550 2352-pyrrolidinyl)-2-thienyl CXXXV MorpholinylNH 5-CONHNMe₂-2-thienyl 482201 CXXXVI MorpholinylNH 5-CONHCH₂CH₂NMe₂- 510 190 2-thienyl CXXXVIIMorpholinylNH 5-CONHCH₂CH₂(1- 536 224 pyrrolidinyl)-2-thienyl CXXXVIIIMorpholinylNH 5-CONHCH₂CH₂(1- 552 241 morpholinyl)-2-thienyl CXXXIXMorpholinylNH 5-CONHmorpholinyl-2-thienyl 524 271 CXL MorpholinylNH5-CONHCH₂CH₂CH₂(1- 564 260 pyrrolidonyl)-2-thienyl CXLI MorpholinylNH5-CONHCH₂CH₂(3- 544 203 pyridyl)-2-thienyl CXLII MorpholinylNH5-CONHCH₂CH₂CH₂(1- 547 263 imidazolyl)-2-thienyl CXLIII MorpholinylNH5-CONHCH₂CH₂(2- 544 >280 pyridyl)-2-thienyl CXLIV MorpholinylNH5-CONHCH₂(3- 530 239 pyridyl)-2-thienyl CXLV MorpholinylNH5-CONHCH₂CH₂(1- 550 228 piperidinyl)-2-thienyl CXLVI Methyl 4-CF₃C₆H₄370 >300 (M − H) CXLVII MorpholinylNH 4-(4-Boc- 574 242 piperazinyl)C₆H₄CXLVIII MorpholinylNH 4-(piperazinyl)C₆H₄ 474 263 CXLIX NH₂4-(piperazinyl)C₆H₄ 389 257 CL NH₂NH 4-(piperazinyl)C₆H₄ 404 257 CLIMe₂NCH₂ 4-(piperazinyl)C₆H₄ 431 243 CLII morpholinylCH₂4-(piperazinyl)C₆H₄ 473 259 CLIII 4-Me-piperazinylCH₂4-(piperazinyl)C₆H₄ 486 NA CLIV 4-NH₂CH₂- 4-(piperazinyl)C₆H₄ 500 239piperidinylCH₂ CLV MorpholinylNH 4-(4-Me- 488 245 piperazinyl)C₆H₄ CLVIMorpholinylNH 4-(4-Et- 502 245 piperazinyl)C₆H₄ CLVII MorpholinylNH4-(4-i-Pr- 516 253 piperazinyl)C₆H₄ CLVIII C₆H₅C(O)NHNH 4-MeOC₆H₄459 >300 CLIX 4-pyridylC(O)NHNH 4-MeOC₆H₄ 455 248 CLX 3-pyridylC(O)NHNH4-MeOC₆H₄ 455 227 CLXI 3,4-dihydroxy- 4-MeOC₆H₄ 486 >300 C₆H₃C(O)NHNHCLXII 4-hydroxy- 4-MeOC₆H₄ 470 283 C₆H₄C(O)NHNH CLXIII3-amino-C₆H₄C(O)NHNH 4-MeOC₆H₄ 469 250 CLXIV 4-amino-C₆H₄C(O)NHNH4-MeOC₆H₄ 469 247 CLXV 2-amino-C₆H₄C(O)NHNH 4-MeOC₆H₄ 469 257 CLXVI4-N,N-dimethylamino- 4-MeOC₆H₄ 497 259 C₆H₄C(O)NHNH CLXVIIC₆H₅CH₂C(O)NHNH 4-MeOC₆H₄ 468 269 CLXVIII 2-hydroxy- 4-MeOC₆H₄ 470 280C₆H₄C(O)NHNH CLXIX MeOC(O)NHNH 4-MeOC₆H₄ 408 >300

TABLE 2

Example Number R¹ R² 100 2-pyridylmethyl 4-MeOC₆H₄ 101 2-pyridylmethyl3-MeOC₆H₄ 102 2-pyridylmethyl 4-NH₂C₆H₄ 103 2-pyridylmethyl 3-NH₂C₆H₄104 2-pyridylmethyl 2-NH₂C₆H₄ 105 2-pyridylmethyl 4-Me₂NC₆H₄ 1062-pyridylmethyl 3-Me₂NC₆H₄ 107 2-pyridylmethyl 2-Me₂NC₆H₄ 1082-pyridylmethyl 4-pyridyl 109 2-pyridylmethyl 3-pyridyl 1102-pyridylmethyl 2-pyridyl 111 2-pyridylmethyl 2-thiazolyl 1122-pyridylmethyl 2-pyrazolyl 113 2-pyridylmethyl 5-isoquinolyl 1142-pyridylmethyl 3,4-methylenedioxyC₆H₃ 115 2-pyridylmethyl3,4-ethylenedioxyC₆H₃ 116 2-pyridylmethyl 2-imidazolyl 1172-pyridylmethyl 2-oxazolyl 118 2-pyridylmethyl 4-isoxazolyl 1192-pyridylmethyl 4-HOC₆H₄ 120 2-pyridylmethyl 3-HOC₆H₄ 1212-pyridylmethyl 3,4-diHOC₆H₄ 122 2-pyridylmethyl 4-NH₂CH₂C₆H₄ 1232-pyridylmethyl 3-NH₂CH₂C₆H₄ 124 3-pyridylmethyl 4-MeOC₆H₄ 1253-pyridylmethyl 3-MeOC₆H₄ 126 3-pyridylmethyl 4-NH₂C₆H₄ 1273-pyridylmethyl 3-NH₂C₆H₄ 128 3-pyridylmethyl 2-NH₂C₆H₄ 1293-pyridylmethyl 4-Me₂NC₆H₄ 130 3-pyridylmethyl 3-Me₂NC₆H₄ 1313-pyridylmethyl 2-Me₂NC₆H₄ 132 3-pyridylmethyl 4-pyridyl 1333-pyridylmethyl 3-pyridyl 134 3-pyridylmethyl 2-pyridyl 1353-pyridylmethyl 2-thiazolyl 136 3-pyridylmethyl 2-pyrazolyl 1373-pyridylmethyl 5-isoquinolyl 138 3-pyridylmethyl 3,4-methylenedioxyC₆H₃139 3-pyridylmethyl 3,4-ethylenedioxyC₆H₃ 140 3-pyridylmethyl2-imidazolyl 141 3-pyridylmethyl 2-oxazolyl 142 3-pyridylmethyl4-isoxazolyl 143 3-pyridylmethyl 4-HOC₆H₄ 144 3-pyridylmethyl 3-HOC₆H₄145 3-pyridylmethyl 3,4-diHOC₆H₄ 146 3-pyridylmethyl 4-NH₂CH₂C₆H₄ 1473-pyridylmethyl 3-NH₂CH₂C₆H₄ 148 4-pyridylmethyl 4-MeOC₆H₄ 1494-pyridylmethyl 3-MeOC₆H₄ 150 4-pyridylmethyl 4-NH₂C₆H₄ 1514-pyridylmethyl 3-NH₂C₆H₄ 152 4-pyridylmethyl 2-NH₂C₆H₄ 1534-pyridylmethyl 4-Me₂NC₆H₄ 154 4-pyridylmethyl 3-Me₂NC₆H₄ 1554-pyridylmethyl 2-Me₂NC₆H₄ 156 4-pyridylmethyl 4-pyridyl 1574-pyridylmethyl 3-pyridyl 158 4-pyridylmethyl 2-pyridyl 1594-pyridylmethyl 2-thiazolyl 160 4-pyridylmethyl 2-pyrazolyl 1614-pyridylmethyl 5-isoquinolyl 162 4-pyridylmethyl 3,4-methylenedioxyC₆H₃163 4-pyridylmethyl 3,4-ethylenedioxyC₆H₃ 164 4-pyridylmethyl2-imidazolyl 165 4-pyridylmethyl 2-oxazolyl 166 4-pyridylmethyl4-isoxazolyl 167 4-pyridylmethyl 4-HOC₆H₄ 168 4-pyridylmethyl 3-HOC₆H₄169 4-pyridylmethyl 3,4-diHOC₆H₄ 170 4-pyridylmethyl 4-NH₂CH₂C₆H₄ 1714-pyridylmethyl 3-NH₂CH₂C₆H₄ 172 2-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 173 2-NH₂C₆H₄CH₂3-MeOC₆H₄ 174 2-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 175 2-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1762-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 177 2-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 178 2-NH₂C₆H₄CH₂3-Me₂NC₆H₄ 179 2-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 180 2-NH₂C₆H₄CH₂ 4-pyridyl 1812-NH₂C₆H₄CH₂ 3-pyridyl 182 2-NH₂C₆H₄CH₂ 2-pyridyl 183 2-NH₂C₆H₄CH₂2-thiazolyl 184 2-NH₂C₆H₄CH₂ 2-pyrazolyl 185 2-NH₂C₆H₄CH₂ 5-isoquinolyl186 2-NH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 187 2-NH₂C₆H₄CH₂3,4-ethylenedioxyC₆H₃ 188 2-NH₂C₆H₄CH₂ 2-imidazolyl 189 2-NH₂C₆H₄CH₂2-oxazolyl 190 2-NH₂C₆H₄CH₂ 4-isoxazolyl 191 2-NH₂C₆H₄CH₂ 4-HOC₆H₄ 1922-NH₂C₆H₄CH₂ 3-HOC₆H₄ 193 2-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 194 2-NH₂C₆H₄CH₂4-NH₂CH₂C₆H₄ 195 2-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 196 3-NH₂C₆H₄CH₂ 3-MeOC₆H₄197 3-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 198 3-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 199 3-NH₂C₆H₄CH₂2-NH₂C₆H₄ 200 3-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 201 3-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 2023-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 203 3-NH₂C₆H₄CH₂ 4-pyridyl 204 3-NH₂C₆H₄CH₂3-pyridyl 205 3-NH₂C₆H₄CH₂ 2-pyridyl 206 3-NH₂C₆H₄CH₂ 2-thiazolyl 2073-NH₂C₆H₄CH₂ 2-pyrazolyl 208 3-NH₂C₆H₄CH₂ 5-isoquinolyl 209 3-NH₂C₆H₄CH₂3,4-methylenedioxyC₆H₃ 210 3-NH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 2113-NH₂C₆H₄CH₂ 2-imidazolyl 212 3-NH₂C₆H₄CH₂ 2-oxazolyl 213 3-NH₂C₆H₄CH₂4-isoxazolyl 214 3-NH₂C₆H₄CH₂ 4-HOC₆H₄ 215 3-NH₂C₆H₄CH₂ 3-HOC₆H₄ 2163-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 217 3-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 218 3-NH₂C₆H₄CH₂3-NH₂CH₂C₆H₄ 219 4-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 220 4-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 2214-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 222 4-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 223 4-NH₂C₆H₄CH₂4-Me₂NC₆H₄ 224 4-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 225 4-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 2264-NH₂C₆H₄CH₂ 4-pyridyl 227 4-NH₂C₆H₄CH₂ 3-pyridyl 228 4-NH₂C₆H₄CH₂2-pyridyl 229 4-NH₂C₆H₄CH₂ 2-thiazolyl 230 4-NH₂C₆H₄CH₂ 2-pyrazolyl 2314-NH₂C₆H₄CH₂ 5-isoquinolyl 232 4-NH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 2334-NH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 234 4-NH₂C₆H₄CH₂ 2-imidazolyl 2354-NH₂C₆H₄CH₂ 2-oxazolyl 236 4-NH₂C₆H₄CH₂ 4-isoxazolyl 237 4-NH₂C₆H₄CH₂4-HOC₆H₄ 238 4-NH₂C₆H₄CH₂ 3-HOC₆H₄ 239 4-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 2404-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 241 4-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 242 2-MeOC₆H₄CH₂3-MeOC₆H₄ 243 2-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 244 2-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 2452-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 246 2-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 247 2-MeOC₆H₄CH₂3-Me₂NC₆H₄ 248 2-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 249 2-MeOC₆H₄CH₂ 4-pyridyl 2502-MeOC₆H₄CH₂ 3-pyridyl 251 2-MeOC₆H₄CH₂ 2-pyridyl 252 2-MeOC₆H₄CH₂2-thiazolyl 253 2-MeOC₆H₄CH₂ 2-pyrazolyl 254 2-MeOC₆H₄CH₂ 5-isoquinolyl255 2-MeOC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 256 2-MeOC₆H₄CH₂3,4-ethylenedioxyC₆H₃ 257 2-MeOC₆H₄CH₂ 2-imidazolyl 258 2-MeOC₆H₄CH₂2-oxazolyl 259 2-MeOC₆H₄CH₂ 4-isoxazolyl 260 2-MeOC₆H₄CH₂ 4-HOC₆H₄ 2612-MeOC₆H₄CH₂ 3-HOC₆H₄ 262 2-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 263 2-MeOC₆H₄CH₂4-NH₂CH₂C₆H₄ 264 2-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 265 3-MeOC₆H₄CH₂ 3-MeOC₆H₄266 3-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 267 3-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 268 3-MeOC₆H₄CH₂2-NH₂C₆H₄ 269 3-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 270 3-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 2713-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 272 3-MeOC₆H₄CH₂ 4-pyridyl 273 3-MeOC₆H₄CH₂3-pyridyl 274 3-MeOC₆H₄CH₂ 2-pyridyl 275 3-MeOC₆H₄CH₂ 2-thiazolyl 2763-MeOC₆H₄CH₂ 2-pyrazolyl 277 3-MeOC₆H₄CH₂ 5-isoquinolyl 278 3-MeOC₆H₄CH₂3,4-methylenedioxyC₆H₃ 279 3-MeOC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 2803-MeOC₆H₄CH₂ 2-imidazolyl 281 3-MeOC₆H₄CH₂ 2-oxazolyl 282 3-MeOC₆H₄CH₂4-isoxazolyl 283 3-MeOC₆H₄CH₂ 4-HOC₆H₄ 284 3-MeOC₆H₄CH₂ 3-HOC₆H₄ 2853-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 286 3-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 287 3-MeOC₆H₄CH₂3-NH₂CH₂C₆H₄ 288 4-MeOC₆H₄CH₂ 3-MeOC₆H₄ 289 4-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 2904-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 291 4-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 292 4-MeOC₆H₄CH₂4-Me₂NC₆H₄ 293 4-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 294 4-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 2954-MeOC₆H₄CH₂ 4-pyridyl 296 4-MeOC₆H₄CH₂ 3-pyridyl 297 4-MeOC₆H₄CH₂2-pyridyl 298 4-MeOC₆H₄CH₂ 2-thiazolyl 299 4-MeOC₆H₄CH₂ 2-pyrazolyl 3004-MeOC₆H₄CH₂ 5-isoquinolyl 301 4-MeOC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 3024-MeOC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 303 4-MeOC₆H₄CH₂ 2-imidazolyl 3044-MeOC₆H_(4CH) ₂ 2-oxazolyl 305 4-MeOC₆H₄CH₂ 4-isoxazolyl 3064-MeOC₆H₄CH₂ 4-HOC₆H₄ 307 4-MeOC₆H₄CH₂ 3-HOC₆H₄ 308 4-MeOC₆H₄CH₂3,4-diHOC₆H₄ 309 4-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 310 4-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄311 2-HOC₆H₄CH₂ 4-MeOC₆H₄ 312 2-HOC₆H₄CH₂ 3-MeOC₆H₄ 313 2-HOC₆H₄CH₂4-NH₂C₆H₄ 314 2-HOC₆H₄CH₂ 3-NH₂C₆H₄ 315 2-HOC₆H₄CH₂ 2-NH₂C₆H₄ 3162-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 317 2-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 318 2-HOC₆H₄CH₂2-Me₂NC₆H₄ 319 2-HOC₆H₄CH₂ 4-pyridyl 320 2-HOC₆H₄CH₂ 3-pyridyl 3212-HOC₆H₄CH₂ 2-pyridyl 322 2-HOC₆H₄CH₂ 2-thiazolyl 323 2-HOC₆H₄CH₂2-pyrazolyl 324 2-HOC₆H₄CH₂ 5-isoquinolyl 325 2-HOC₆H₄CH₂3,4-methylenedioxyC₆H₃ 326 2-HOC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 3272-HOC₆H₄CH₂ 2-imidazolyl 328 2-HOC₆H₄CH₂ 2-oxazolyl 329 2-HOC₆H₄CH₂4-isoxazolyl 330 2-HOC₆H₄CH₂ 4-HOC₆H₄ 331 2-HOC₆H₄CH₂ 3-HOC₆H₄ 3322-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 333 2-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 334 2-HOC₆H₄CH₂3-NH₂CH₂C₆H₄ 335 3-HOC₆H₄CH₂ 4-MeOC₆H₄ 336 3-HOC₆H₄CH₂ 3-MeOC₆H₄ 3373-HOC₆H₄CH₂ 4-NH₂C₆H₄ 338 3-HOC₆H₄CH₂ 3-NH₂C₆H₄ 339 3-HOC₆H₄CH₂2-NH₂C₆H₄ 340 3-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 341 3-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 3423-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 343 3-HOC₆H₄CH₂ 4-pyridyl 344 3-HOC₆H₄CH₂3-pyridyl 345 3-HOC₆H₄CH₂ 2-pyridyl 346 3-HOC₆H₄CH₂ 2-thiazolyl 3473-HOC₆H₄CH₂ 2-pyrazolyl 348 3-HOC₆H₄CH₂ 5-isoquinolyl 349 3-HOC₆H₄CH₂3,4-methylenedioxyC₆H₃ 350 3-HOC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 3513-HOC₆H₄CH₂ 2-imidazolyl 352 3-HOC₆H₄CH₂ 2-oxazolyl 353 3-HOC₆H₄CH₂4-isoxazolyl 354 3-HOC₆H₄CH₂ 4-HOC₆H₄ 355 3-HOC₆H₄CH₂ 3-HOC₆H₄ 3563-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 357 3-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 358 3-HOC₆H₄CH₂3-NH₂CH₂C₆H₄ 359 4-HOC₆H₄CH₂ 4-MeOC₆H₄ 360 4-HOC₆H₄CH₂ 3-MeOC₆H₄ 3614-HOC₆H₄CH₂ 4-NH₂C₆H₄ 362 4-HOC₆H₄CH₂ 3-NH₂C₆H₄ 363 4-HOC₆H₄CH₂2-NH₂C₆H₄ 364 4-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 365 4-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 3664-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 367 4-HOC₆H₄CH₂ 4-pyridyl 368 4-HOC₆H₄CH₂3-pyridyl 369 4-HOC₆H₄CH₂ 2-pyridyl 370 4-HOC₆H₄CH₂ 2-thiazolyl 3714-HOC₆H₄CH₂ 2-pyrazolyl 372 4-HOC₆H₄CH₂ 5-isoquinolyl 373 4-HOC₆H₄CH₂3,4-methylenedioxyC₆H₃ 374 4-HOC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 3754-HOC₆H₄CH₂ 2-imidazolyl 376 4-HOC₆H₄CH₂ 2-oxazolyl 377 4-HOC₆H₄CH₂4-isoxazolyl 378 4-HOC₆H₄CH₂ 4-HOC₆H₄ 379 4-HOC₆H₄CH₂ 3-HOC₆H₄ 3804-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 381 4-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 382 4-HOC₆H₄CH₂3-NH₂CH₂C₆H₄ 383 4-ClC₆H₄CH₂ 3-MeOC₆H₄ 384 4-ClC₆H₄CH₂ 4-NH₂C₆H₄ 3854-ClC₆H₄CH₂ 3-NH₂C₆H₄ 386 4-ClC₆H₄CH₂ 2-NH₂C₆H₄ 387 4-ClC₆H₄CH₂4-Me₂NC₆H₄ 388 4-ClC₆H₄CH₂ 3-Me₂NC₆H₄ 389 4-ClC₆H₄CH₂ 2-Me₂NC₆H₄ 3904-ClC₆H₄CH₂ 4-pyridyl 391 4-ClC₆H₄CH₂ 3-pyridyl 392 4-ClC₆H₄CH₂2-pyridyl 393 4-ClC₆H₄CH₂ 2-thiazolyl 394 4-ClC₆H₄CH₂ 2-pyrazolyl 3954-ClC₆H₄CH₂ 5-isoquinolyl 396 4-ClC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 3974-ClC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 398 4-ClC₆H₄CH₂ 2-imidazolyl 3994-ClC₆H₄CH₂ 2-oxazolyl 400 4-ClC₆H₄CH₂ 4-isoxazolyl 401 4-ClC₆H₄CH₂4-HOC₆H₄ 402 4-ClC₆H₄CH₂ 3-HOC₆H₄ 403 4-ClC₆H₄CH₂ 3,4-diHOC₆H₄ 4044-ClC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 405 4-ClC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 4062-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 407 2-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 4082-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 409 2-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 4102-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 411 2-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 4122-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 413 2-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 4142-NH₂CH₂C₆H₄CH₂ 4-pyridyl 415 2-NH₂CH₂C₆H₄CH₂ 3-pyridyl 4162-NH₂CH₂C₆H₄CH₂ 2-pyridyl 417 2-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 4182-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 419 2-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 4202-NH₂CH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 421 2-NH₂CH₂C₆H₄CH₂3,4-ethylenedioxyC₆H₃ 422 2-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 4232-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 424 2-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 4252-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 426 2-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 4272-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 428 2-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 4292-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 430 3-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 4313-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 432 3-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 4333-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 434 3-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 4353-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 436 3-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 4373-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 438 3-NH₂CH₂C₆H₄CH₂ 4-pyridyl 4393-NH₂CH₂C₆H₄CH₂ 3-pyridyl 440 3-NH₂CH₂C₆H₄CH₂ 2-pyridyl 4413-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 442 3-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 4433-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 444 3-NH₂CH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃445 3-NH₂CH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 446 3-NH₂CH₂C₆H₄CH₂2-imidazolyl 447 3-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 448 3-NH₂CH₂C₆H₄CH₂4-isoxazolyl 449 3-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 450 3-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄451 3-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 452 3-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 4533-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 454 4-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 4554-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 456 4-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 4574-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 458 4-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 4594-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 460 4-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 4614-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 462 4-NH₂CH₂C₆H₄CH₂ 4-pyridyl 4634-NH₂CH₂C₆H₄CH₂ 3-pyridyl 464 4-NH₂CH₂C₆H₄CH₂ 2-pyridyl 4654-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 466 4-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 4674-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 468 4-NH₂CH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃469 4-NH₂CH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 470 4-NH₂CH₂C₆H₄CH₂2-imidazolyl 471 4-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 472 4-NH₂CH₂C₆H₄CH₂4-isoxazolyl 473 4-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 474 4-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄475 4-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 476 4-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 4774-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 478 2-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 4792-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 480 2-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 4812-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 482 2-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 4832-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 484 2-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 4852-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 486 2-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 4872-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 488 2-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 4892-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 490 2-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 4912-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 492 2-Me₂NCH₂C₆H₄CH₂3,4-methylenedioxyC₆H₃ 493 2-Me₂NCH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 4942-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 495 2-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 4962-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 497 2-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 4982-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 499 2-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 5002-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 501 2-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 5023-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 503 3-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 5043-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 505 3-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 5063-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 507 3-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 5083-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 509 3-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 5103-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 511 3-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 5123-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 513 3-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 5143-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 515 3-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 5163-Me₂NCH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 517 3-Me₂NCH₂C₆H₄CH₂3,4-ethylenedioxyC₆H₃ 518 3-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 5193-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 520 3-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 5213-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 522 3-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 5233-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 524 3-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 5253-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 526 4-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 5274-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 528 4-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 5294-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 530 4-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 5314-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 532 4-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 5334-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 534 4-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 5354-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 536 4-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 5374-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 538 4-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 5394-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 540 4-Me₂NCH₂C₆H₄CH₂3,4-methylenedioxyC₆H₃ 541 4-Me₂NCH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 5424-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 543 4-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 5454-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 546 4-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 5474-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 548 4-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 5494-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 550 4-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 551 H3-MeOC₆H₄ 552 H 4-NH₂C₆H₄ 553 H 3-NH₂C₆H₄ 554 H 2-NH₂C₆H₄ 555 H4-Me₂NC₆H₄ 556 H 3-Me₂NC₆H₄ 557 H 2-Me₂NC₆H₄ 558 H 3-pyridyl 559 H2-pyridyl 560 H 2-thiazolyl 561 H 2-pyrazolyl 562 H 5-isoquinolyl 563 H3,4-methylenedioxyC₆H₃ 564 H 3,4-ethylenedioxyC₆H₃ 565 H 2-imidazolyl566 H 2-oxazolyl 567 H 4-isoxazolyl 568 H 4-HOC₆H₄ 569 H 3-HOC₆H₄ 570 H3,4-diHOC₆H₄ 571 H 4-NH₂CH₂C₆H₄ 572 H 3-NH₂CH₂C₆H₄ 573 Me 3-MeOC₆H₄ 574Me 4-NH₂C₆H₄ 575 Me 3-NH₂C₆H₄ 576 Me 2-NH₂C₆H₄ 577 Me 4-Me₂NC₆H₄ 578 Me3-Me₂NC₆H₄ 579 Me 2-Me₂NC₆H₄ 580 Me 3-pyridyl 581 Me 2-pyridyl 582 Me2-thiazolyl 583 Me 2-pyrazolyl 584 Me 5-isoquinolyl 585 Me3,4-ethylenedioxyC₆H₃ 586 Me 2-imidazolyl 587 Me 2-oxazolyl 588 Me4-isoxazolyl 589 Me 3-HOC₆H₄ 590 Me 3,4-diHOC₆H₄ 591 Me 4-NH₂CH₂C₆H₄ 592Me 3-NH₂CH₂C₆H₄ 593 Et 3-MeOC₆H₄ 594 Et 4-NH₂C₆H₄ 595 Et 3-NH₂C₆H₄ 596Et 2-NH₂C₆H₄ 597 Et 4-Me₂NC₆H₄ 598 Et 3-Me₂NC₆H₄ 599 Et 2-Me₂NC₆H₄ 600Et 4-pyridyl 601 Et 3-pyridyl 602 Et 2-pyridyl 603 Et 2-thiazolyl 604 Et2-pyrazolyl 605 Et 5-isoquinolyl 606 Et 3,4-methylenedioxyC₆H₃ 607 Et3,4-ethylenedioxyC₆H₃ 608 Et 2-imidazolyl 609 Et 2-oxazolyl 610 Et4-isoxazolyl 611 Et 4-HOC₆H₄ 612 Et 3-HOC₆H₄ 613 Et 3,4-diHOC₆H₄ 614 Et4-NH₂CH₂C₆H₄ 615 Et 3-NH₂CH₂C₆H₄ 616 Me₂NCH₂ 3-MeOC₆H₄ 617 Me₂NCH₂4-NH₂C₆H₄ 618 Me₂NCH₂ 3-NH₂C₆H₄ 619 Me₂NCH₂ 2-NH₂C₆H₄ 620 Me₂NCH₂4-Me₂NC₆H₄ 621 Me₂NCH₂ 3-Me₂NC₆H₄ 622 Me₂NCH₂ 2-Me₂NC₆H₄ 623 Me₂NCH₂4-pyridyl 624 Me₂NCH₂ 3-pyridyl 625 Me₂NCH₂ 2-pyridyl 626 Me₂NCH₂2-thiazolyl 627 Me₂NCH₂ 2-pyrazolyl 628 Me₂NCH₂ 5-isoquinolyl 629Me₂NCH₂ 3,4-methylenedioxyC₆H₃ 630 Me₂NCH₂ 3,4-ethylenedioxyC₆H₃ 631Me₂NCH₂ 2-imidazolyl 632 Me₂NCH₂ 2-oxazolyl 633 Me₂NCH₂ 4-isoxazolyl 634Me₂NCH₂ 4-HOC₆H₄ 635 Me₂NCH₂ 3-HOC₆H₄ 636 Me₂NCH₂ 3,4-diHOC₆H₄ 637Me₂NCH₂ 4-NH₂CH₂C₆H₄ 638 Me₂NCH₂ 3-NH₂CH₂C₆H₄ 639 EtNHCH₂ 3-MeOC₆H₄ 640EtNHCH₂ 4-NH₂C₆H₄ 641 EtNHCH₂ 3-NH₂C₆H₄ 642 EtNHCH₂ 2-NH₂C₆H₄ 643EtNHCH₂ 4-Me₂NC₆H₄ 644 EtNHCH₂ 3-Me₂NC₆H₄ 645 EtNHCH₂ 2-Me₂NC₆H₄ 646EtNHCH₂ 4-pyridyl 647 EtNHCH₂ 3-pyridyl 648 EtNHCH₂ 2-pyridyl 649EtNHCH₂ 2-thiazolyl 650 EtNHCH₂ 2-pyrazolyl 651 EtNHCH₂ 5-isoquinolyl652 EtNHCH₂ 3,4-methylenedioxyC₆H₃ 653 EtNHCH₂ 3,4-ethylenedioxyC₆H₃ 654EtNHCH₂ 2-imidazolyl 655 EtNHCH₂ 2-oxazolyl 656 EtNHCH₂ 4-isoxazolyl 657EtNHCH₂ 4-HOC₆H₄ 658 EtNHCH₂ 3-HOC₆H₄ 659 EtNHCH₂ 3,4-diHOC₆H₄ 660EtNHCH₂ 4-NH₂CH₂C₆H₄ 661 EtNHCH₂ 3-NH₂CH₂C₆H₄ 662 HOCH₂CH₂NHCH₂3-MeOC₆H₄ 663 HOCH₂CH₂NHCH₂ 4-NH₂C₆H₄ 664 HOCH₂CH₂NHCH₂ 3-NH₂C₆H₄ 665HOCH₂CH₂NHCH₂ 2-NH₂C₆H₄ 666 HOCH₂CH₂NHCH₂ 4-Me₂NC₆H₄ 667 HOCH₂CH₂NHCH₂3-Me₂NC₆H₄ 668 HOCH₂CH₂NHCH₂ 2-Me₂NC₆H₄ 669 HOCH₂CH₂NHCH₂ 4-pyridyl 670HOCH₂CH₂NHCH₂ 3-pyridyl 671 HOCH₂CH₂NHCH₂ 2-pyridyl 672 HOCH₂CH₂NHCH₂2-thiazolyl 673 HOCH₂CH₂NHCH₂ 2-pyrazolyl 674 HOCH₂CH₂NHCH₂5-isoquinolyl 675 HOCH₂CH₂NHCH₂ 3,4-methylenedioxyC₆H₃ 676 HOCH₂CH₂NHCH₂3,4-ethylenedioxyC₆H₃ 677 HOCH₂CH₂NHCH₂ 2-imidazolyl 678 HOCH₂CH₂NHCH₂2-oxazolyl 679 HOCH₂CH₂NHCH₂ 4-isoxazolyl 680 HOCH₂CH₂NHCH₂ 4-HOC₆H₄ 681HOCH₂CH₂NHCH₂ 3-HOC₆H₄ 682 HOCH₂CH₂NHCH₂ 3,4-diHOC₆H₄ 683 HOCH₂CH₂NHCH₂4-NH₂CH₂C₆H₄ 684 HOCH₂CH₂NHCH₂ 3-NH₂CH₂C₆H₄ 685 H₂NCH₂CH₂NHCH₂ 4-MeOC₆H₄686 H₂NCH₂CH₂NHCH₂ 3-MeOC₆H₄ 687 H₂NCH₂CH₂NHCH₂ 4-NH₂C₆H₄ 688H₂NCH₂CH₂NHCH₂ 3-NH₂C₆H₄ 689 H₂NCH₂CH₂NHCH₂ 2-NH₂C₆H₄ 690 H₂NCH₂CH₂NHCH₂4-Me₂NC₆H₄ 691 H₂NCH₂CH₂NHCH₂ 3-Me₂NC₆H₄ 692 H₂NCH₂CH₂NHCH₂ 2-Me₂NC₆H₄693 H₂NCH₂CH₂NHCH₂ 4-pyridyl 694 H₂NCH₂CH₂NHCH₂ 3-pyridyl 695H₂NCH₂CH₂NHCH₂ 2-pyridyl 696 H₂NCH₂CH₂NHCH₂ 2-thiazolyl 697H₂NCH₂CH₂NHCH₂ 2-pyrazolyl 698 H₂NCH₂CH₂NHCH₂ 5-isoquinolyl 699H₂NCH₂CH₂NHCH₂ 3,4-methylenedioxyC₆H₃ 700 H₂NCH₂CH₂NHCH₂3,4-ethylenedioxyC₆H₃ 701 H₂NCH₂CH₂NHCH₂ 2-imidazolyl 702 H₂NCH₂CH₂NHCH₂2-oxazolyl 703 H₂NCH₂CH₂NHCH₂ 4-isoxazolyl 704 H₂NCH₂CH₂NHCH₂ 4-HOC₆H₄705 H₂NCH₂CH₂NHCH₂ 3-HOC₆H₄ 706 H₂NCH₂CH₂NHCH₂ 3,4-diHOC₆H₄ 707H₂NCH₂CH₂NHCH₂ 4-NH₂CH₂C₆H₄ 708 H₂NCH₂CH₂NHCH₂ 3-NH₂CH₂C₆H₄ 709Me₂NCH₂CH₂NHCH₂ 4-MeOC₆H₄ 710 Me₂NCH₂CH₂NHCH₂ 3-MeOC₆H₄ 711Me₂NCH₂CH₂NHCH₂ 4-NH₂C₆H₄ 712 Me₂NCH₂CH₂NHCH₂ 3-NH₂C₆H₄ 713Me₂NCH₂CH₂NHCH₂ 2-NH₂C₆H₄ 714 Me₂NCH₂CH₂NHCH₂ 4-Me₂NC₆H₄ 715Me₂NCH₂CH₂NHCH₂ 3-Me₂NC₆H₄ 716 Me₂NCH₂CH₂NHCH₂ 2-Me₂NC₆H₄ 717Me₂NCH₂CH₂NHCH₂ 4-pyridyl 718 Me₂NCH₂CH₂NHCH₂ 3-pyridyl 719Me₂NCH₂CH₂NHCH₂ 2-pyridyl 720 Me₂NCH₂CH₂NHCH₂ 2-thiazolyl 721Me₂NCH₂CH₂NHCH₂ 2-pyrazolyl 722 Me₂NCH₂CH₂NHCH₂ 5-isoquinolyl 723Me₂NCH₂CH₂NHCH₂ 3,4-methylenedioxyC₆H₃ 724 Me₂NCH₂CH₂NHCH₂3,4-ethylenedioxyC₆H₃ 725 Me₂NCH₂CH₂NHCH₂ 2-imidazolyl 726Me₂NCH₂CH₂NHCH₂ 2-oxazolyl 727 Me₂NCH₂CH₂NHCH₂ 4-isoxazolyl 728Me₂NCH₂CH₂NHCH₂ 4-HOC₆H₄ 729 Me₂NCH₂CH₂NHCH₂ 3-HOC₆H₄ 730Me₂NCH₂CH₂NHCH₂ 3,4-diHOC₆H₄ 731 Me₂NCH₂CH₂NHCH₂ 4-NH₂CH₂C₆H₄ 732Me₂NCH₂CH₂NHCH₂ 3-NH₂CH₂C₆H₄ 733 1-morpholinylmethyl 3-MeOC₆H₄ 7341-morpholinylmethyl 4-NH₂C₆H₄ 735 1-morpholinylmethyl 3-NH₂C₆H₄ 7361-morpholinylmethyl 2-NH₂C₆H₄ 737 1-morpholinylmethyl 4-Me₂NC₆H₄ 7381-morpholinylmethyl 3-Me₂NC₆H₄ 739 1-morpholinylmethyl 2-Me₂NC₆H₄ 7401-morpholinylmethyl 4-pyridyl 741 1-morpholinylmethyl 3-pyridyl 7421-morpholinylmethyl 2-pyridyl 743 1-morpholinylmethyl 2-thiazolyl 7441-morpholinylmethyl 2-pyrazolyl 745 1-morpholinylmethyl 5-isoquinolyl746 1-morpholinylmethyl 3,4-methylenedioxyC₆H₃ 747 1-morpholinylmethyl3,4-ethylenedioxyC₆H₃ 748 1-morpholinylmethyl 2-imidazolyl 7491-morpholinylmethyl 2-oxazolyl 750 1-morpholinylmethyl 4-isoxazolyl 7511-morpholinylmethyl 4-HOC₆H₄ 752 1-morpholinylmethyl 3-HOC₆H₄ 7531-morpholinylmethyl 3,4-diHOC₆H₄ 754 1-morpholinylmethyl 4-NH₂CH₂C₆H₄755 1-morpholinylmethyl 3-NH₂CH₂C₆H₄ 756 1-thiomorpholinylmethyl3-MeOC₆H₄ 757 1-thiomorpholinylmethyl 4-NH₂C₆H₄ 7581-thiomorpholinylmethyl 3-NH₂C₆H₄ 759 1-thiomorpholinylmethyl 2-NH₂C₆H₄760 1-thiomorpholinylmethyl 4-Me₂NC₆H₄ 761 1-thiomorpholinylmethyl3-Me₂NC₆H₄ 762 1-thiomorpholinylmethyl 2-Me₂NC₆H₄ 7631-thiomorpholinylmethyl 4-pyridyl 764 1-thiomorpholinylmethyl 3-pyridyl765 1-thiomorpholinylmethyl 2-pyridyl 766 1-thiomorpholinylmethyl2-thiazolyl 767 1-thiomorpholinylmethyl 2-pyrazolyl 7681-thiomorpholinylmethyl 5-isoquinolyl 769 1-thiomorpholinylmethyl3,4-methylenedioxyC₆H₃ 770 1-thiomorpholinylmethyl 3,4-ethylenedioxyC₆H₃771 1-thiomorpholinylmethyl 2-imidazolyl 772 1-thiomorpholinylmethyl2-oxazolyl 773 1-thiomorpholinylmethyl 4-isoxazolyl 7741-thiomorpholinylmethyl 4-HOC₆H₄ 775 1-thiomorpholinylmethyl 3-HOC₆H₄776 1-thiomorpholinylmethyl 3,4-diHOC₆H₄ 777 1-thiomorpholinylmethyl4-NH₂CH₂C₆H₄ 778 1-thiomorpholinylmethyl 3-NH₂CH₂C₆H₄ 7791-piperazinylmethyl 3-MeOC₆H₄ 780 1-piperazinylmethyl 4-NH₂C₆H₄ 7811-piperazinylmethyl 3-NH₂C₆H₄ 782 1-piperazinylmethyl 2-NH₂C₆H₄ 7831-piperazinylmethyl 4-Me₂NC₆H₄ 784 1-piperazinylmethyl 3-Me₂NC₆H₄ 7851-piperazinylmethyl 2-Me₂NC₆H₄ 786 1-piperazinylmethyl 4-pyridyl 7871-piperazinylmethyl 3-pyridyl 788 1-piperazinylmethyl 2-pyridyl 7891-piperazinylmethyl 2-thiazolyl 790 1-piperazinylmethyl 2-pyrazolyl 7911-piperazinylmethyl 5-isoquinolyl 792 1-piperazinylmethyl3,4-methylenedioxyC₆H₃ 793 1-piperazinylmethyl 3,4-ethylenedioxyC₆H₃ 7941-piperazinylmethyl 2-imidazolyl 795 1-piperazinylmethyl 2-oxazolyl 7961-piperazinylmethyl 4-isoxazolyl 797 1-piperazinylmethyl 4-HOC₆H₄ 7981-piperazinylmethyl 3-HOC₆H₄ 799 1-piperazinylmethyl 3,4-diHOC₆H₄ 8001-piperazinylmethyl 4-NH₂CH₂C₆H₄ 801 1-piperazinylmethyl 3-NH₂CH₂C₆H₄

TABLE 3

Example Number R¹ R² 802 2-pyridylmethyl 4-MeOC₆H₄ 803 2-pyridylmethyl3-MeOC₆H₄ 804 2-pyridylmethyl 4-NH₂C₆H₄ 805 2-pyridylmethyl 3-NH₂C₆H₄806 2-pyridylmethyl 2-NH₂C₆H₄ 807 2-pyridylmethyl 4-Me₂NC₆H₄ 8082-pyridylmethyl 3-Me₂NC₆H₄ 809 2-pyridylmethyl 2-Me₂NC₆H₄ 8102-pyridylmethyl 4-pyridyl 811 2-pyridylmethyl 3-pyridyl 8122-pyridylmethyl 2-pyridyl 813 2-pyridylmethyl 2-thiazolyl 8142-pyridylmethyl 2-pyrazolyl 815 2-pyridylmethyl 5-isoquinolyl 8162-pyridylmethyl 3,4-methylenedioxyC₆H₃ 817 2-pyridylmethyl3,4-ethylenedioxyC₆H₃ 818 2-pyridylmethyl 2-imidazolyl 8192-pyridylmethyl 2-oxazolyl 820 2-pyridylmethyl 4-isoxazolyl 8212-pyridylmethyl 4-HOC₆H₄ 822 2-pyridylmethyl 3-HOC₆H₄ 8232-pyridylmethyl 3,4-diHOC₆H₄ 824 2-pyridylmethyl 4-NH₂CH₂C₆H₄ 8252-pyridylmethyl 3-NH₂CH₂C₆H₄ 826 3-pyridylmethyl 4-MeOC₆H₄ 8273-pyridylmethyl 3-MeOC₆H₄ 828 3-pyridylmethyl 4-NH₂C₆H₄ 8293-pyridylmethyl 3-NH₂C₆H₄ 830 3-pyridylmethyl 2-NH₂C₆H₄ 8313-pyridylmethyl 4-Me₂NC₆H₄ 832 3-pyridylmethyl 3-Me₂NC₆H₄ 8333-pyridylmethyl 2-Me₂NC₆H₄ 834 3-pyridylmethyl 4-pyridyl 8353-pyridylmethyl 3-pyridyl 836 3-pyridylmethyl 2-pyridyl 8373-pyridylmethyl 2-thiazolyl 838 3-pyridylmethyl 2-pyrazolyl 8393-pyridylmethyl 5-isoquinolyl 840 3-pyridylmethyl 3,4-methylenedioxyC₆H₃841 3-pyridylmethyl 3,4-ethylenedioxyC₆H₃ 842 3-pyridylmethyl2-imidazolyl 843 3-pyridylmethyl 2-oxazolyl 844 3-pyridylmethyl4-isoxazolyl 845 3-pyridylmethyl 4-HOC₆H₄ 846 3-pyridylmethyl 3-HOC₆H₄847 3-pyridylmethyl 3,4-diHOC₆H₄ 848 3-pyridylmethyl 4-NH₂CH₂C₆H₄ 8493-pyridylmethyl 3-NH₂CH₂C₆H₄ 850 4-pyridylmethyl 4-MeOC₆H₄ 8514-pyridylmethyl 3-MeOC₆H₄ 852 4-pyridylmethyl 4-NH₂C₆H₄ 8534-pyridylmethyl 3-NH₂C₆H₄ 854 4-pyridylmethyl 2-NH₂C₆H₄ 8554-pyridylmethyl 4-Me₂NC₆H₄ 856 4-pyridylmethyl 3-Me₂NC₆H₄ 8574-pyridylmethyl 2-Me₂NC₆H₄ 858 4-pyridylmethyl 4-pyridyl 8594-pyridylmethyl 3-pyridyl 860 4-pyridylmethyl 2-pyridyl 8614-pyridylmethyl 2-thiazolyl 862 4-pyridylmethyl 2-pyrazolyl 8634-pyridylmethyl 5-isoquinolyl 864 4-pyridylmethyl 3,4-methylenedioxyC₆H₃865 4-pyridylmethyl 3,4-ethylenedioxyC₆H₃ 866 4-pyridylmethyl2-imidazolyl 867 4-pyridylmethyl 2-oxazolyl 868 4-pyridylmethyl4-isoxazolyl 869 4-pyridylmethyl 4-HOC₆H₄ 870 4-pyridylmethyl 3-HOC₆H₄871 4-pyridylmethyl 3,4-diHOC₆H₄ 872 4-pyridylmethyl 4-NH₂CH₂C₆H₄ 8734-pyridylmethyl 3-NH₂CH₂C₆H₄ 874 2-NH₂C₆H₄ 4-MeOC₆H₄ 875 2-NH₂C₆H₄3-MeOC₆H₄ 876 2-NH₂C₆H₄ 4-NH₂C₆H₄ 877 2-NH₂C₆H₄ 3-NH₂C₆H₄ 878 2-NH₂C₆H₄2-NH₂C₆H₄ 879 2-NH₂C₆H₄ 4-Me₂NC₆H₄ 880 2-NH₂C₆H₄ 3-Me₂NC₆H₄ 8812-NH₂C₆H₄ 2-Me₂NC₆H₄ 882 2-NH₂C₆H₄ 4-pyridyl 883 2-NH₂C₆H₄ 3-pyridyl 8842-NH₂C₆H₄ 2-pyridyl 885 2-NH₂C₆H₄ 2-thiazolyl 886 2-NH₂C₆H₄ 2-pyrazolyl887 2-NH₂C₆H₄ 5-isoquinolyl 888 2-NH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 8892-NH₂C₆H₄ 3,4-ethylenedioxyC₆H₃ 890 2-NH₂C₆H₄ 2-imidazolyl 891 2-NH₂C₆H₄2-oxazolyl 892 2-NH₂C₆H₄ 4-isoxazolyl 893 2-NH₂C₆H₄ 4-HOC₆H₄ 8942-NH₂C₆H₄ 3-HOC₆H₄ 895 2-NH₂C₆H₄ 3,4-diHOC₆H₄ 896 2-NH₂C₆H₄ 4-NH₂CH₂C₆H₄897 2-NH₂C₆H₄ 3-NH₂CH₂C₆H₄ 898 3-NH₂C₆H₄ 4-MeOC₆H₄ 899 3-NH₂C₆H₄3-MeOC₆H₄ 900 3-NH₂C₆H₄ 4-NH₂C₆H₄ 901 3-NH₂C₆H₄ 3-NH₂C₆H₄ 902 3-NH₂C₆H₄2-NH₂C₆H₄ 903 3-NH₂C₆H₄ 4-Me₂NC₆H₄ 904 3-NH₂C₆H₄ 3-Me₂NC₆H₄ 9053-NH₂C₆H₄ 2-Me₂NC₆H₄ 906 3-NH₂C₆H₄ 4-pyridyl 907 3-NH₂C₆H₄ 3-pyridyl 9083-NH₂C₆H₄ 2-pyridyl 909 3-NH₂C₆H₄ 2-thiazolyl 910 3-NH₂C₆H₄ 2-pyrazolyl911 3-NH₂C₆H₄ 5-isoquinolyl 912 3-NH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 9133-NH₂C₆H₄ 3,4-ethylenedioxyC₆H₃ 914 3-NH₂C₆H₄ 2-imidazolyl 915 3-NH₂C₆H₄2-oxazolyl 916 3-NH₂C₆H₄ 4-isoxazolyl 917 3-NH₂C₆H₄ 4-HOC₆H₄ 9183-NH₂C₆H₄ 3-HOC₆H₄ 919 3-NH₂C₆H₄ 3,4-diHOC₆H₄ 920 3-NH₂C₆H₄ 4-NH₂CH₂C₆H₄921 3-NH₂C₆H₄ 3-NH₂CH₂C₆H₄ 922 4-NH₂C₆H₄ 4-MeOC₆H₄ 923 4-NH₂C₆H₄3-MeOC₆H₄ 924 4-NH₂C₆H₄ 4-NH₂C₆H₄ 925 4-NH₂C₆H₄ 3-NH₂C₆H₄ 926 4-NH₂C₆H₄2-NH₂C₆H₄ 927 4-NH₂C₆H₄ 4-Me₂NC₆H₄ 928 4-NH₂C₆H₄ 3-Me₂NC₆H₄ 9304-NH₂C₆H₄ 2-Me₂NC₆H₄ 931 4-NH₂C₆H₄ 4-pyridyl 932 4-NH₂C₆H₄ 3-pyridyl 9334-NH₂C₆H₄ 2-pyridyl 934 4-NH₂C₆H₄ 2-thiazolyl 935 4-NH₂C₆H₄ 2-pyrazolyl936 4-NH₂C₆H₄ 5-isoquinolyl 937 4-NH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 9384-NH₂C₆H₄ 3,4-ethylenedioxyC₆H₃ 939 4-NH₂C₆H₄ 2-imidazolyl 940 4-NH₂C₆H₄2-oxazolyl 941 4-NH₂C₆H₄ 4-isoxazolyl 942 4-NH₂C₆H₄ 4-HOC₆H₄ 9434-NH₂C₆H₄ 3-HOC₆H₄ 944 4-NH₂C₆H₄ 3,4-diHOC₆H₄ 945 4-NH₂C₆H₄ 4-NH₂CH₂C₆H₄946 4-NH₂C₆H₄ 3-NH₂CH₂C₆H₄ 947 2-MeOC₆H₄ 4-MeOC₆H₄ 948 2-MeOC₆H₄3-MeOC₆H₄ 949 2-MeOC₆H₄ 4-NH₂C₆H₄ 950 2-MeOC₆H₄ 3-NH₂C₆H₄ 951 2-MeOC₆H₄2-NH₂C₆H₄ 952 2-MeOC₆H₄ 4-Me₂NC₆H₄ 953 2-MeOC₆H₄ 3-Me₂NC₆H₄ 9542-MeOC₆H₄ 2-Me₂NC₆H₄ 955 2-MeOC₆H₄ 4-pyridyl 956 2-MeOC₆H₄ 3-pyridyl 9572-MeOC₆H₄ 2-pyridyl 958 2-MeOC₆H₄ 2-thiazolyl 959 2-MeOC₆H₄ 2-pyrazolyl960 2-MeOC₆H₄ 5-isoquinolyl 961 2-MeOC₆H₄ 3,4-methylenedioxyC₆H₃ 9622-MeOC₆H₄ 3-4-ethylenedioxyC₆H₃ 963 2-MeOC₆H₄ 2-imidazolyl 964 2-MeOC₆H₄2-oxazolyl 965 2-MeOC₆H₄ 4-isoxazolyl 966 2-MeOC₆H₄ 4-HOC₆H₄ 9672-MeOC₆H₄ 3-HOC₆H₄ 968 2-MeOC₆H₄ 3,4-diHOC₆H₄ 969 2-MeOC₆H₄ 4-NH₂CH₂C₆H₄970 2-MeOC₆H₄ 3-NH₂CH₂C₆H₄ 971 3-MeOC₆H₄ 4-MeOC₆H₄ 972 3-MeOC₆H₄3-MeOC₆H₄ 973 3-MeOC₆H₄ 4-NH₂C₆H₄ 974 3-MeOC₆H₄ 3-NH₂C₆H₄ 975 3-MeOC₆H₄2-NH₂C₆H₄ 976 3-MeOC₆H₄ 4-Me₂NC₆H₄ 977 3-MeOC₆H₄ 3-Me₂NC₆H₄ 9783-MeOC₆H₄ 2-Me₂NC₆H₄ 979 3-MeOC₆H₄ 4-pyridyl 980 3-MeOC₆H₄ 3-pyridyl 9813-MeOC₆H₄ 2-pyridyl 982 3-MeOC₆H₄ 2-thiazolyl 983 3-MeOC₆H₄ 2-pyrazolyl984 3-MeOC₆H₄ 5-isoquinolyl 985 3-MeOC₆H₄ 3,4-methylenedioxyC₆H₃ 9863-MeOC₆H₄ 3,4-ethylenedioxyC₆H₃ 987 3-MeOC₆H₄ 2-imidazolyl 988 3-MeOC₆H₄2-oxazolyl 989 3-MeOC₆H₄ 4-isoxazolyl 990 3-MeOC₆H₄ 4-HOC₆H₄ 9913-MeOC₆H₄ 3-HOC₆H₄ 992 3-MeOC₆H₄ 3,4-diHOC₆H₄ 993 3-MeOC₆H₄ 4-NH₂CH₂C₆H₄994 3-MeOC₆H₄ 3-NH₂CH₂C₆H₄ 995 4-MeOC₆H₄ 4-MeOC₆H₄ 996 4-MeOC₆H₄3-MeOC₆H₄ 997 4-MeOC₆H₄ 4-NH₂C₆H₄ 998 4-MeOC₆H₄ 3-NH₂C₆H₄ 999 4-MeOC₆H₄2-NH₂C₆H₄ 1000 4-MeOC₆H₄ 4-Me₂NC₆H₄ 1001 4-MeOC₆H₄ 3-Me₂NC₆H₄ 10024-MeOC₆H₄ 2-Me₂NC₆H₄ 1003 4-MeOC₆H₄ 4-pyridyl 1004 4-MeOC₆H₄ 3-pyridyl1005 4-MeOC₆H₄ 2-pyridyl 1006 4-MeOC₆H₄ 2-thiazolyl 1007 4-MeOC₆H₄2-pyrazolyl 1008 4-MeOC₆H₄ 5-isoquinolyl 1009 4-MeOC₆H₄3,4-methylenedioxyC₆H₃ 1010 4-MeOC₆H₄ 3,4-ethylenedioxyC₆H₃ 10114-MeOC₆H₄ 2-imidazolyl 1012 4-MeOC₆H₄ 2-oxazolyl 1013 4-MeOC₆H₄4-isoxazolyl 1014 4-MeOC₆H₄ 4-HOC₆H₄ 1015 4-MeOC₆H₄ 3-HOC₆H₄ 10164-MeOC₆H₄ 3,4-diHOC₆H₄ 1017 4-MeOC₆H₄ 4-NH₂CH₂C₆H₄ 1018 4-MeOC₆H₄3-NH₂CH₂C₆H₄ 1019 2-HOC₆H₄ 4-MeOC₆H₄ 1020 2-HOC₆H₄ 3-MeOC₆H₄ 10212-HOC₆H₄ 4-NH₂C₆H₄ 1022 2-HOC₆H₄ 3-NH₂C₆H₄ 1023 2-HOC₆H₄ 2-NH₂C₆H₄ 10242-HOC₆H₄ 4-Me₂NC₆H₄ 1025 2-HOC₆H₄ 3-Me₂NC₆H₄ 1026 2-HOC₆H₄ 2-Me₂NC₆H₄1027 2-HOC₆H₄ 4-pyridyl 1028 2-HOC₆H₄ 3-pyridyl 1029 2-HOC₆H₄ 2-pyridyl1030 2-HOC₆H₄ 2-thiazolyl 1031 2-HOC₆H₄ 2-pyrazolyl 1032 2-HOC₆H₄5-isoquinolyl 1033 2-HOC₆H₄ 3,4-methylenedioxyC₆H₃ 1034 2-HOC₆H₄3,4-ethylenedioxyC₆H₃ 1035 2-HOC₆H₄ 2-imidazolyl 1036 2-HOC₆H₄2-oxazolyl 1037 2-HOC₆H₄ 4-isoxazolyl 1038 2-HOC₆H₄ 4-HOC₆H₄ 10392-HOC₆H₄ 3-HOC₆H₄ 1040 2-HOC₆H₄ 3,4-diHOC₆H₄ 1041 2-HOC₆H₄ 4-NH₂CH₂C₆H₄1042 2-HOC₆H₄ 3-NH₂CH₂C₆H₄ 1043 3-HOC₆H₄ 4-MeOC₆H₄ 1044 3-HOC₆H₄3-MeOC₆H₄ 1045 3-HOC₆H₄ 4-NH₂C₆H₄ 1046 3-HOC₆H₄ 3-NH₂C₆H₄ 1047 3-HOC₆H₄2-NH₂C₆H₄ 1048 3-HOC₆H₄ 4-Me₂NC₆H₄ 1049 3-HOC₆H₄ 3-Me₂NC₆H₄ 10503-HOC₆H₄ 2-Me₂NC₆H₄ 1051 3-HOC₆H₄ 4-pyridyl 1052 3-HOC₆H₄ 3-pyridyl 10533-HOC₆H₄ 2-pyridyl 1054 3-HOC₆H₄ 2-thiazolyl 1055 3-HOC₆H₄ 2-pyrazolyl1056 3-HOC₆H₄ 5-isoquinolyl 1057 3-HOC₆H₄ 3,4-methylenedioxyC₆H₃ 10583-HOC₆H₄ 3,4-ethylenedioxyC₆H₃ 1059 3-HOC₆H₄ 2-imidazolyl 1060 3-HOC₆H₄2-oxazolyl 1061 3-HOC₆H₄ 4-isoxazolyl 1062 3-HOC₆H₄ 4-HOC₆H₄ 10633-HOC₆H₄ 3-HOC₆H₄ 1064 3-HOC₆H₄ 3,4-diHOC₆H₄ 1065 3-HOC₆H₄ 4-NH₂CH₂C₆H₄1066 3-HOC₆H₄ 3-NH₂CH₂C₆H₄ 1067 4-HOC₆H₄ 4-MeOC₆H₄ 1068 4-HOC₆H₄3-MeOC₆H₄ 1069 4-HOC₆H₄ 4-NH₂C₆H₄ 1070 4-HOC₆H₄ 3-NH₂C₆H₄ 1071 4-HOC₆H₄2-NH₂C₆H₄ 1072 4-HOC₆H₄ 4-Me₂NC₆H₄ 1073 4-HOC₆H₄ 3-Me₂NC₆H₄ 10744-HOC₆H₄ 2-Me₂NC₆H₄ 1075 4-HOC₆H₄ 4-pyridyl 1076 4-HOC₆H₄ 3-pyridyl 10774-HOC₆H₄ 2-pyridyl 1078 4-HOC₆H₄ 2-thiazolyl 1079 4-HOC₆H₄ 2-pyrazolyl1080 4-HOC₆H₄ 5-isoquinolyl 1081 4-HOC₆H₄ 3,4-methylenedioxyC₆H₃ 10824-HOC₆H₄ 3,4-ethylenedioxyC₆H₃ 1083 4-HOC₆H₄ 2-imidazolyl 1084 4-HOC₆H₄2-oxazolyl 1085 4-HOC₆H₄ 4-isoxazolyl 1086 4-HOC₆H₄ 4-HOC₆H₄ 10874-HOC₆H₄ 3-HOC₆H₄ 1088 4-HOC₆H₄ 3,4-diHOC₆H₄ 1089 4-HOC₆H₄ 4-NH₂CH₂C₆H₄1090 4-HOC₆H₄ 3-NH₂CH₂C₆H₄ 1091 4-ClC₆H₄ 4-MeOC₆H₄ 1092 4-ClC₆H₄3-MeOC₆H₄ 1093 4-ClC₆H₄ 4-NH₂C₆H₄ 1094 4-ClC₆H₄ 3-NH₂C₆H₄ 1095 4-ClC₆H₄2-NH₂C₆H₄ 1096 4-ClC₆H₄ 4-Me₂NC₆H₄ 1097 4-ClC₆H₄ 3-Me₂NC₆H₄ 10984-ClC₆H₄ 2-Me₂NC₆H₄ 1099 4-ClC₆H₄ 4-pyridyl 1100 4-ClC₆H₄ 3-pyridyl 11014-ClC₆H₄ 2-pyridyl 1102 4-ClC₆H₄ 2-thiazolyl 1103 4-ClC₆H₄ 2-pyrazolyl1104 4-ClC₆H₄ 5-isoquinolyl 1105 4-ClC₆H₄ 3,4-methylenedioxyC₆H₃ 11064-ClC₆H₄ 3,4-ethylenedioxyC₆H₃ 1107 4-ClC₆H₄ 2-imidazolyl 1108 4-ClC₆H₄2-oxazolyl 1109 4-ClC₆H₄ 4-isoxazolyl 1110 4-ClC₆H₄ 4-HOC₆H₄ 11114-ClC₆H₄ 3-HOC₆H₄ 1112 4-ClC₆H₄ 3,4-diHOC₆H₄ 1113 4-ClC₆H₄ 4-NH₂CH₂C₆H₄1114 4-ClC₆H₄ 3-NH₂CH₂C₆H₄ 1115 2-NH₂CH₂C₆H₄ 4-MeOC₆H₄ 1116 2-NH₂CH₂C₆H₄3-MeOC₆H₄ 1117 2-NH₂CH₂C₆H₄ 4-NH₂C₆H₄ 1118 2-NH₂CH₂C₆H₄ 3-NH₂C₆H₄ 11192-NH₂CH₂C₆H₄ 2-NH₂C₆H₄ 1120 2-NH₂CH₂C₆H₄ 4-Me₂NC₆H₄ 1121 2-NH₂CH₂C₆H₄3-Me₂NC₆H₄ 1122 2-NH₂CH₂C₆H₄ 2-Me₂NC₆H₄ 1123 2-NH₂CH₂C₆H₄ 4-pyridyl 11242-NH₂CH₂C₆H₄ 3-pyridyl 1125 2-NH₂CH₂C₆H₄ 2-pyridyl 1126 2-NH₂CH₂C₆H₄2-thiazolyl 1127 2-NH₂CH₂C₆H₄ 2-pyrazolyl 1128 2-NH₂CH₂C₆H₄5-isoquinolyl 1129 2-NH₂CH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 1130 2-NH₂CH₂C₆H₄3,4-ethylenedioxyC₆H₃ 1131 2-NH₂CH₂C₆H₄ 2-imidazolyl 1132 2-NH₂CH₂C₆H₄2-oxazolyl 1133 2-NH₂CH₂C₆H₄ 4-isoxazolyl 1134 2-NH₂CH₂C₆H₄ 4-HOC₆H₄1135 2-NH₂CH₂C₆H₄ 3-HOC₆H₄ 1136 2-NH₂CH₂C₆H₄ 3,4-diHOC₆H₄ 11372-NH₂CH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1138 2-NH₂CH₂C₆H₄ 3-NH₂CH₂C₆H₄ 11393-NH₂CH₂C₆H₄ 4-MeOC₆H₄ 1140 3-NH₂CH₂C₆H₄ 3-MeOC₆H₄ 1141 3-NH₂CH₂C₆H₄4-NH₂C₆H₄ 1142 3-NH₂CH₂C₆H₄ 3-NH₂C₆H₄ 1143 3-NH₂CH₂C₆H₄ 2-NH₂C₆H₄ 11443-NH₂CH₂C₆H₄ 4-Me₂NC₆H₄ 1145 3-NH₂CH₂C₆H₄ 3-Me₂NC₆H₄ 1146 3-NH₂CH₂C₆H₄2-Me₂NC₆H₄ 1147 3-NH₂CH₂C₆H₄ 4-pyridyl 1148 3-NH₂CH₂C₆H₄ 3-pyridyl 11493-NH₂CH₂C₆H₄ 2-pyridyl 1150 3-NH₂CH₂C₆H₄ 2-thiazolyl 1151 3-NH₂CH₂C₆H₄2-pyrazolyl 1152 3-NH₂CH₂C₆H₄ 5-isoquinolyl 1153 3-NH₂CH₂C₆H₄3,4-methylenedioxyC₆H₃ 1154 3-NH₂CH₂C₆H₄ 3,4-ethylenedioxyC₆H₃ 11553-NH₂CH₂C₆H₄ 2-imidazolyl 1156 3-NH₂CH₂C₆H₄ 2-oxazolyl 1157 3-NH₂CH₂C₆H₄4-isoxazolyl 1158 3-NH₂CH₂C₆H₄ 4-HOC₆H₄ 1159 3-NH₂CH₂C₆H₄ 3-HOC₆H₄ 11603-NH₂CH₂C₆H₄ 3,4-diHOC₆H₄ 1161 3-NH₂CH₂C₆H₄ 4-NH₂CH₂C₆H₄ 11623-NH₂CH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1163 4-NH₂CH₂C₆H₄ 4-MeOC₆H₄ 1164 4-NH₂CH₂C₆H₄3-MeOC₆H₄ 1165 4-NH₂CH₂C₆H₄ 4-NH₂C₆H₄ 1166 4-NH₂CH₂C₆H₄ 3-NH₂C₆H₄ 11674-NH₂CH₂C₆H₄ 2-NH₂C₆H₄ 1168 4-NH₂CH₂C₆H₄ 4-Me₂NC₆H₄ 1169 4-NH₂CH₂C₆H₄3-Me₂NC₆H₄ 1170 4-NH₂CH₂C₆H₄ 2-Me₂NC₆H₄ 1171 4-NH₂CH₂C₆H₄ 4-pyridyl 11724-NH₂CH₂C₆H₄ 3-pyridyl 1173 4-NH₂CH₂C₆H₄ 2-pyridyl 1174 4-NH₂CH₂C₆H₄2-thiazolyl 1175 4-NH₂CH₂C₆H₄ 2-pyrazolyl 1176 4-NH₂CH₂C₆H₄5-isoquinolyl 1177 4-NH₂CH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 1178 4-NH₂CH₂C₆H₄3,4-ethylenedioxyC₆H₃ 1179 4-NH₂CH₂C₆H₄ 2-imidazolyl 1180 4-NH₂CH₂C₆H₄2-oxazolyl 1181 4-NH₂CH₂C₆H₄ 4-isoxazolyl 1182 4-NH₂CH₂C₆H₄ 4-HOC₆H₄1183 4-NH₂CH₂C₆H₄ 3-HOC₆H₄ 1184 4-NH₂CH₂C₆H₄ 3,4-diHOC₆H₄ 11854-NH₂CH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1186 4-NH₂CH₂C₆H₄ 3-NH₂CH₂C₆H₄ 11872-Me₂NCH₂C₆H₄ 4-MeOC₆H₄ 1188 2-Me₂NCH₂C₆H₄ 3-MeOC₆H₄ 1189 2-Me₂NCH₂C₆H₄4-NH₂C₆H₄ 1190 2-Me₂NCH₂C₆H₄ 3-NH₂C₆H₄ 1191 2-Me₂NCH₂C₆H₄ 2-NH₂C₆H₄ 11922-Me₂NCH₂C₆H₄ 4-Me₂NC₆H₄ 1193 2-Me₂NCH₂C₆H₄ 3-Me₂NC₆H₄ 11942-Me₂NCH₂C₆H₄ 2-Me₂NC₆H₄ 1195 2-Me₂NCH₂C₆H₄ 4-pyridyl 1196 2-Me₂NCH₂C₆H₄3-pyridyl 1197 2-Me₂NCH₂C₆H₄ 2-pyridyl 1198 2-Me₂NCH₂C₆H₄ 2-thiazolyl1199 2-Me₂NCH₂C₆H₄ 2-pyrazolyl 1200 2-Me₂NCH₂C₆H₄ 5-isoquinolyl 12012-Me₂NCH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 1202 2-Me₂NCH₂C₆H₄3,4-ethylenedioxyC₆H₃ 1203 2-Me₂NCH₂C₆H₄ 2-imidazolyl 1204 2-Me₂NCH₂C₆H₄2-oxazolyl 1205 2-Me₂NCH₂C₆H₄ 4-isoxazolyl 1206 2-Me₂NCH₂C₆H₄ 4-HOC₆H₄1207 2-Me₂NCH₂C₆H₄ 3-HOC₆H₄ 1208 2-Me₂NCH₂C₆H₄ 3,4-diHOC₆H₄ 12092-Me₂NCH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1210 2-Me₂NCH₂C₆H₄ 3-NH₂CH₂C₆H₄ 12113-Me₂NCH₂C₆H₄ 4-MeOC₆H₄ 1212 3-Me₂NCH₂C₆H₄ 3-MeOC₆H₄ 1213 3-Me₂NCH₂C₆H₄4-NH₂C₆H₄ 1214 3-Me₂NCH₂C₆H₄ 3-NH₂C₆H₄ 1215 3-Me₂NCH₂C₆H₄ 2-NH₂C₆H₄ 12163-Me₂NCH₂C₆H₄ 4-Me₂NC₆H₄ 1217 3-Me₂NCH₂C₆H₄ 3-Me₂NC₆H₄ 12183-Me₂NCH₂C₆H₄ 2-Me₂NC₆H₄ 1219 3-Me₂NCH₂C₆H₄ 4-pyridyl 1220 3-Me₂NCH₂C₆H₄3-pyridyl 1221 3-Me₂NCH₂C₆H₄ 2-pyridyl 1222 3-Me₂NCH₂C₆H₄ 2-thiazolyl1223 3-Me₂NCH₂C₆H₄ 2-pyrazolyl 1224 3-Me₂NCH₂C₆H₄ 5-isoquinolyl 12253-Me₂NCH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 1226 3-Me₂NCH₂C₆H₄3,4-ethylenedioxyC₆H₃ 1227 3-Me₂NCH₂C₆H₄ 2-imidazolyl 1228 3-Me₂NCH₂C₆H₄2-oxazolyl 1229 3-Me₂NCH₂C₆H₄ 4-isoxazolyl 1230 3-Me₂NCH₂C₆H₄ 4-HOC₆H₄1231 3-Me₂NCH₂C₆H₄ 3-HOC₆H₄ 1232 3-Me₂NCH₂C₆H₄ 3,4-diHOC₆H₄ 12333-Me₂NCH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1234 3-Me₂NCH₂C₆H₄ 3-NH₂CH₂C₆H₄ 12354-Me₂NCH₂C₆H₄ 4-MeOC₆H₄ 1236 4-Me₂NCH₂C₆H₄ 3-MeOC₆H₄ 1237 4-Me₂NCH₂C₆H₄4-NH₂C₆H₄ 1238 4-Me₂NCH₂C₆H₄ 3-NH₂C₆H₄ 1239 4-Me₂NCH₂C₆H₄ 2-NH₂C₆H₄ 12404-Me₂NCH₂C₆H₄ 4-Me₂NC₆H₄ 1241 4-Me₂NCH₂C₆H₄ 3-Me₂NC₆H₄ 12424-Me₂NCH₂C₆H₄ 2-Me₂NC₆H₄ 1243 4-Me₂NCH₂C₆H₄ 4-pyridyl 1244 4-Me₂NCH₂C₆H₄3-pyridyl 1245 4-Me₂NCH₂C₆H₄ 2-pyridyl 1246 4-Me₂NCH₂C₆H₄ 2-thiazolyl1247 4-Me₂NCH₂C₆H₄ 2-pyrazolyl 1248 4-Me₂NCH₂C₆H₄ 5-isoquinolyl 12494-Me₂NCH₂C₆H₄ 3,4-methylenedioxyC₆H₃ 1250 4-Me₂NCH₂C₆H₄3,4-ethylenedioxyC₆H₃ 1251 4-Me₂NCH₂C₆H₄ 2-imidazolyl 1252 4-Me₂NCH₂C₆H₄2-oxazolyl 1253 4-Me₂NCH₂C₆H₄ 4-isoxazolyl 1254 4-Me₂NCH₂C₆H₄ 4-HOC₆H₄1255 4-Me₂NCH₂C₆H₄ 3-HOC₆H₄ 1256 4-Me₂NCH₂C₆H₄ 3,4-diHOC₆H₄ 12574-Me₂NCH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1258 4-Me₂NCH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1259 H4-MeOC₆H₄ 1260 H 3-MeOC₆H₄ 1261 H 4-NH₂C₆H₄ 1262 H 3-NH₂C₆H₄ 1263 H2-NH₂C₆H₄ 1264 H 4-Me₂NC₆H₄ 1265 H 3-Me₂NC₆H₄ 1266 H 2-Me₂NC₆H₄ 1267 H4-pyridyl 1268 H 3-pyridyl 1269 H 2-pyridyl 1270 H 2-thiazolyl 1271 H2-pyrazolyl 1272 H 5-isoquinolyl 1273 H 3,4-methylenedioxyC₆H₃ 1274 H3,4-ethylenedioxyC₆H₃ 1275 H 2-imidazolyl 1276 H 2-oxazolyl 1277 H4-isoxazolyl 1278 H 4-HOC₆H₄ 1279 H 3-HOC₆H₄ 1280 H 3,4-diHOC₆H₄ 1281 H4-NH₂CH₂C₆H₄ 1282 H 3-NH₂CH₂C₆H₄ 1283 Me 4-MeOC₆H₄ 1284 Me 3-MeOC₆H₄1285 Me 4-NH₂C₆H₄ 1286 Me 3-NH₂C₆H₄ 1287 Me 2-NH₂C₆H₄ 1288 Me 4-Me₂NC₆H₄1289 Me 3-Me₂NC₆H₄ 1290 Me 2-Me₂NC₆H₄ 1291 Me 4-pyridyl 1292 Me3-pyridyl 1293 Me 2-pyridyl 1294 Me 2-thiazolyl 1295 Me 2-pyrazolyl 1296Me 5-isoquinolyl 1297 Me 3,4-methylenedioxyC₆H₃ 1298 Me3,4-ethylenedioxyC₆H₃ 1299 Me 2-imidazolyl 1300 Me 2-oxazolyl 1301 Me4-isoxazolyl 1302 Me 4-HOC₆H₄ 1303 Me 3-HOC₆H₄ 1304 Me 3,4-diHOC₆H₄ 1305Me 4-NH₂CH₂C₆H₄ 1306 Me 3-NH₂CH₂C₆H₄ 1307 Et 4-MeOC₆H₄ 1308 Et 3-MeOC₆H₄1309 Et 4-NH₂C₆H₄ 1310 Et 3-NH₂C₆H₄ 1311 Et 2-NH₂C₆H₄ 1312 Et 4-Me₂NC₆H₄1313 Et 3-Me₂NC₆H₄ 1314 Et 2-Me₂NC₆H₄ 1315 Et 4-pyridyl 1316 Et3-pyridyl 1317 Et 2-pyridyl 1318 Et 2-thiazolyl 1319 Et 2-pyrazolyl 1320Et 5-isoquinolyl 1321 Et 3,4-methylenedioxyC₆H₃ 1322 Et3,4-ethylenedioxyC₆H₃ 1323 Et 2-imidazolyl 1324 Et 2-oxazolyl 1325 Et4-isoxazolyl 1326 Et 4-HOC₆H₄ 1327 Et 3-HOC₆H₄ 1328 Et 3,4-diHOC₆H₄ 1329Et 4-NH₂CH₂C₆H₄ 1330 Et 3-NH₂CH₂C₆H₄ 1331 2-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 13322-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 1333 2-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1334 2-NH₂C₆H₄CH₂3-NH₂C₆H₄ 1335 2-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1336 2-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 13372-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1338 2-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1339 2-NH₂C₆H₄CH₂4-pyridyl 1340 2-NH₂C₆H₄CH₂ 3-pyridyl 1341 2-NH₂C₆H₄CH₂ 2-pyridyl 13422-NH₂C₆H₄CH₂ 2-thiazolyl 1343 2-NH₂C₆H₄CH₂ 2-pyrazolyl 1344 2-NH₂C₆H₄CH₂5-isoquinolyl 1345 2-NH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1346 2-NH₂C₆H₄CH₂3-4-ethylenedioxyC₆H₃ 1347 2-NH₂C₆H₄CH₂ 2-imidazolyl 1348 2-NH₂C₆H₄CH₂2-oxazolyl 1349 2-NH₂C₆H₄CH₂ 4-isoxazolyl 1350 2-NH₂C₆H₄CH₂ 4-HOC₆H₄1351 2-NH₂C₆H₄CH₂ 3-HOC₆H₄ 1352 2-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 13532-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1354 2-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 13553-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 1356 3-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 1357 3-NH₂C₆H₄CH₂4-NH₂C₆H₄ 1358 3-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1359 3-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 13603-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1361 3-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1362 3-NH₂C₆H₄CH₂2-Me₂NC₆H₄ 1363 3-NH₂C₆H₄CH₂ 4-pyridyl 1364 3-NH₂C₆H₄CH₂ 3-pyridyl 13653-NH₂C₆H₄CH₂ 2-pyridyl 1366 3-NH₂C₆H₄CH₂ 2-thiazolyl 1367 3-NH₂C₆H₄CH₂2-pyrazolyl 1367 3-NH₂C₆H₄CH₂ 5-isoquinolyl 1369 3-NH₂C₆H₄CH₂3,4-methylenedioxyC₆H₃ 1370 3-NH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 13713-NH₂C₆H₄CH₂ 2-imidazolyl 1372 3-NH₂C₆H₄CH₂ 2-oxazolyl 1373 3-NH₂C₆H₄CH₂4-isoxazolyl 1374 3-NH₂C₆H₄CH₂ 4-HOC₆H₄ 1375 3-NH₂C₆H₄CH₂ 3-HOC₆H₄ 13763-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1377 3-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 13783-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1379 4-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 1380 4-NH₂C₆H₄CH₂3-MeOC₆H₄ 1381 4-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1382 4-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 13834-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1384 4-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1385 4-NH₂C₆H₄CH₂3-Me₂NC₆H₄ 1386 4-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1387 4-NH₂C₆H₄CH₂ 4-pyridyl 13884-NH₂C₆H₄CH₂ 3-pyridyl 1389 4-NH₂C₆H₄CH₂ 2-pyridyl 1390 4-NH₂C₆H₄CH₂2-thiazolyl 1391 4-NH₂C₆H₄CH₂ 2-pyrazolyl 1392 4-NH₂C₆H₄CH₂5-isoquinolyl 1393 4-NH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1394 4-NH₂C₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1395 4-NH₂C₆H₄CH₂ 2-imidazolyl 1396 4-NH₂C₆H₄CH₂2-oxazolyl 1397 4-NH₂C₆H₄CH₂ 4-isoxazolyl 1398 4-NH₂C₆H₄CH₂ 4-HOC₆H₄1399 4-NH₂C₆H₄CH₂ 3-HOC₆H₄ 1400 4-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 14014-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1402 4-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 14032-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1404 2-MeOC₆H₄CH₂ 3-MeOC₆H₄ 1405 2-MeOC₆H₄CH₂4-NH₂C₆H₄ 1406 2-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 1407 2-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 14082-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 1409 2-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 1410 2-MeOC₆H₄CH₂2-Me₂NC₆H₄ 1411 2-MeOC₆H₄CH₂ 4-pyridyl 1412 2-MeOC₆H₄CH₂ 3-pyridyl 14132-MeOC₆H₄CH₂ 2-pyridyl 1414 2-MeOC₆H₄CH₂ 2-thiazolyl 1415 2-MeOC₆H₄CH₂2-pyrazolyl 1416 2-MeOC₆H₄CH₂ 5-isoquinolyl 1417 2-MeOC₆H₄CH₂3,4-methylenedioxyC₆H₃ 1418 2-MeOC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 14192-MeOC₆H₄CH₂ 2-imidazolyl 1420 2-MeOC₆H₄CH₂ 2-oxazolyl 1421 2-MeOC₆H₄CH₂4-isoxazolyl 1422 2-MeOC₆H₄CH₂ 4-HOC₆H₄ 1423 2-MeOC₆H₄CH₂ 3-HOC₆H₄ 14242-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 1425 2-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 14262-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1427 3-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1428 3-MeOC₆H₄CH₂3-MeOC₆H₄ 1429 3-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 1430 3-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 14313-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 1432 3-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 1433 3-MeOC₆H₄CH₂3-Me₂NC₆H₄ 1434 3-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 1435 3-MeOC₆H₄CH₂ 4-pyridyl 14363-MeOC₆H₄CH₂ 3-pyridyl 1437 3-MeOC₆H₄CH₂ 2-pyridyl 1438 3-MeOC₆H₄CH₂2-thiazolyl 1439 3-MeOC₆H₄CH₂ 2-pyrazolyl 1440 3-MeOC₆H₄CH₂5-isoquinolyl 1441 3-MeOC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1442 3-MeOC₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1443 3-MeOC₆H₄CH₂ 2-imidazolyl 1444 3-MeOC₆H₄CH₂2-oxazolyl 1445 3-MeOC₆H₄CH₂ 4-isoxazolyl 1446 3-MeOC₆H₄CH₂ 4-HOC₆H₄1447 3-MeOC₆H₄CH₂ 3-HOC₆H₄ 1448 3-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 14493-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1450 3-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 14514-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1452 4-MeOC₆H₄CH₂ 3-MeOC₆H₄ 1453 4-MeOC₆H₄CH₂4-NH₂C₆H₄ 1454 4-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 1455 4-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 14564-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 1457 4-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 1458 4-MeOC₆H₄CH₂2-Me₂NC₆H₄ 1459 4-MeOC₆H₄CH₂ 4-pyridyl 1460 4-MeOC₆H₄CH₂ 3-pyridyl 14614-MeOC₆H₄CH₂ 2-pyridyl 1462 4-MeOC₆H₄CH₂ 2-thiazolyl 1463 4-MeOC₆H₄CH₂2-pyrazolyl 1464 4-MeOC₆H₄CH₂ 5-isoquinolyl 1465 4-MeOC₆H₄CH₂3,4-methylenedioxyC₆H₃ 1466 4-MeOC₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 14674-MeOC₆H₄CH₂ 2-imidazolyl 1468 4-MeOC₆H₄CH₂ 2-oxazolyl 1469 4-MeOC₆H₄CH₂4-isoxazolyl 1470 4-MeOC₆H₄CH₂ 4-HOC₆H₄ 1471 4-MeOC₆H₄CH₂ 3-HOC₆H₄ 14724-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 1473 4-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 14744-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1475 2-HOC₆H₄CH₂ 4-MeOC₆H₄ 1476 2-HOC₆H₄CH₂3-MeOC₆H₄ 1477 2-HOC₆H₄CH₂ 4-NH₂C₆H₄ 1478 2-HOC₆H₄CH₂ 3-NH₂C₆H₄ 14792-HOC₆H₄CH₂ 2-NH₂C₆H₄ 1480 2-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 1481 2-HOC₆H₄CH₂3-Me₂NC₆H₄ 1482 2-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 1483 2-HOC₆H₄CH₂ 4-pyridyl 14842-HOC₆H₄CH₂ 3-pyridyl 1485 2-HOC₆H₄CH₂ 2-pyridyl 1486 2-HOC₆H₄CH₂2-thiazolyl 1487 2-HOC₆H₄CH₂ 2-pyrazolyl 1488 2-HOC₆H₄CH₂ 5-isoquinolyl1489 2-HOC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1490 2-HOC₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1491 2-HOC₆H₄CH₂ 2-imidazolyl 1492 2-HOC₆H₄CH₂2-oxazolyl 1493 2-HOC₆H₄CH₂ 4-isoxazolyl 1494 2-HOC₆H₄CH₂ 4-HOC₆H₄ 14952-HOC₆H₄CH₂ 3-HOC₆H₄ 1496 2-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 1497 2-HOC₆H₄CH₂4-NH₂CH₂C₆H₄ 1498 2-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1499 3-HOC₆H₄CH₂ 4-MeOC₆H₄1500 3-HOC₆H₄CH₂ 3-MeOC₆H₄ 1501 3-HOC₆H₄CH₂ 4-NH₂C₆H₄ 1502 3-HOC₆H₄CH₂3-NH₂C₆H₄ 1503 3-HOC₆H₄CH₂ 2-NH₂C₆H₄ 1504 3-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 15053-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 1506 3-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 1507 3-HOC₆H₄CH₂4-pyridyl 1508 3-HOC₆H₄CH₂ 3-pyridyl 1509 3-HOC₆H₄CH₂ 2-pyridyl 15103-HOC₆H₄CH₂ 2-thiazolyl 1511 3-HOC₆H₄CH₂ 2-pyrazolyl 1512 3-HOC₆H₄CH₂5-isoquinolyl 1513 3-HOC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1514 3-HOC₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1514 3-HOC₆H₄CH₂ 2-imidazolyl 1516 3-HOC₆H₄CH₂2-oxazolyl 1517 3-HOC₆H₄CH₂ 4-isoxazolyl 1518 3-HOC₆H₄CH₂ 4-HOC₆H₄ 15193-HOC₆H₄CH₂ 3-HOC₆H₄ 1520 3-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 1521 3-HOC₆H₄CH₂4-NH₂CH₂C₆H₄ 1522 3-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1523 4-HOC₆H₄CH₂ 4-MeOC₆H₄1524 4-HOC₆H₄CH₂ 3-MeOC₆H₄ 1525 4-HOC₆H₄CH₂ 4-NH₂C₆H₄ 1526 4-HOC₆H₄CH₂3-NH₂C₆H₄ 1527 4-HOC₆H₄CH₂ 2-NH₂C₆H₄ 1528 4-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 15294-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 1530 4-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 1531 4-HOC₆H₄CH₂4-pyridyl 1532 4-HOC₆H₄CH₂ 3-pyridyl 1533 4-HOC₆H₄CH₂ 2-pyridyl 15344-HOC₆H₄CH₂ 2-thiazolyl 1535 4-HOC₆H₄CH₂ 2-pyrazolyl 1536 4-HOC₆H₄CH₂5-isoquinolyl 1537 4-HOC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1538 4-HOC₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1539 4-HOC₆H₄CH₂ 2-imidazolyl 1540 4-HOC₆H₄CH₂2-oxazolyl 1541 4-HOC₆H₄CH₂ 4-isoxazolyl 1542 4-HOC₆H₄CH₂ 4-HOC₆H₄ 15434-HOC₆H₄CH₂ 3-HOC₆H₄ 1544 4-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 1545 4-HOC₆H₄CH₂4-NH₂CH₂C₆H₄ 1546 4-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1547 4-ClC₆H₄CH₂ 4-MeOC₆H₄1548 4-ClC₆H₄CH₂ 3-MeOC₆H₄ 1549 4-ClC₆H₄CH₂ 4-NH₂C₆H₄ 1550 4-ClC₆H₄CH₂3-NH₂C₆H₄ 1551 4-ClC₆H₄CH₂ 2-NH₂C₆H₄ 1552 4-ClC₆H₄CH₂ 4-Me₂NC₆H₄ 15534-ClC₆H₄CH₂ 3-Me₂NC₆H₄ 1554 4-ClC₆H₄CH₂ 2-Me₂NC₆H₄ 1555 4-ClC₆H₄CH₂4-pyridyl 1556 4-ClC₆H₄CH₂ 3-pyridyl 1557 4-ClC₆H₄CH₂ 2-pyridyl 15584-ClC₆H₄CH₂ 2-thiazolyl 1559 4-ClC₆H₄CH₂ 2-pyrazolyl 1560 4-ClC₆H₄CH₂5-isoquinolyl 1561 4-ClC₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1562 4-ClC₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1563 4-ClC₆H₄CH₂ 2-imidazolyl 1564 4-ClC₆H₄CH₂2-oxazolyl 1565 4-ClC₆H₄CH₂ 4-isoxazolyl 1566 4-ClC₆H₄CH₂ 4-HOC₆H₄ 15674-ClC₆H₄CH₂ 3-HOC₆H₄ 1568 4-ClC₆H₄CH₂ 3,4-diHOC₆H₄ 1569 4-ClC₆H₄CH₂4-NH₂CH₂C₆H₄ 1570 4-ClC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1571 2-NH₂CH₂C₆H₄CH₂4-MeOC₆H₄ 1572 2-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 1573 2-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄1574 2-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1575 2-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 15762-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1577 2-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 15782-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1579 2-NH₂CH₂C₆H₄CH₂ 4-pyridyl 15802-NH₂CH₂C₆H₄CH₂ 3-pyridyl 1581 2-NH₂CH₂C₆H₄CH₂ 2-pyridyl 15822-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 1583 2-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 15842-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 1585 2-NH₂CH₂C₆H₄CH₂3,4-methylenedioxyC₆H₃ 1586 2-NH₂CH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 15872-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 1588 N-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 15892-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 1590 2-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 15912-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 1592 2-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 15932-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1594 2-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 15953-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 1596 3-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 15973-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1598 3-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 15993-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1600 3-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 16013-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1602 3-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 16033-NH₂CH₂C₆H₄CH₂ 4-pyridyl 1604 3-NH₂CH₂C₆H₄CH₂ 3-pyridyl 16053-NH₂CH₂C₆H₄CH₂ 2-pyridyl 1606 3-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 16073-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 1608 3-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 16093-NH₂CH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1610 3-NH₂CH₂C₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1611 3-NH₂CH₂C₆H_(4CH) ₂ 2-imidazolyl 16123-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 1613 3-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 16143-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 1615 3-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 16163-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1617 3-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 16183-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1619 4-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 16204-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 1621 4-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 16224-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1623 4-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 16244-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1625 4-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 16264-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1627 4-NH₂CH₂C₆H₄CH₂ 4-pyridyl 16284-NH₂CH₂C₆H₄CH₂ 3-pyridyl 1629 4-NH₂CH₂C₆H₄CH₂ 2-pyridyl 16304-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 1631 4-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 16324-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 1633 4-NH₂CH₂C₆H₄CH₂3,4-methylenedioxyC₆H₃ 1634 4-NH₂CH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 16354-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 1636 4-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 16374-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 1638 4-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 16394-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 1640 4-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 16414-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1642 4-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 16432-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 1644 2-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 16452-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1646 2-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 16472-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1648 2-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 16492-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1650 2-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 16512-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 1652 2-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 16532-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 1654 2-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 16552-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 1656 2-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 16572-Me₂NCH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1658 2-Me₂NCH₂C₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1659 2-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 16602-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 1661 2-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 16622-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 1663 2-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 16642-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1665 2-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 16662-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1667 3-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 16683-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 1669 3-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 16703-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1671 3-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 16723-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1673 3-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 16743-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1675 3-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 16763-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 1677 3-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 16783-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 1679 3-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 16803-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 1681 3-Me₂NCH₂C₆H₄CH₂3,4-methylenedioxyC₆H₃ 1682 3-Me₂NCH₂C₆H₄CH₂ 3,4-ethylenedioxyC₆H₃ 16833-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 1684 3-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 16853-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 1686 3-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 16873-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 1688 3-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 16893-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1690 3-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 16914-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 1692 4-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 16934-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1694 4-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 16954-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1696 4-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 16974-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1698 4-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 16994-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 1700 4-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 17014-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 1702 4-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 17034-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 1704 4-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 17054-Me₂NCH₂C₆H₄CH₂ 3,4-methylenedioxyC₆H₃ 1706 4-Me₂NCH₂C₆H₄CH₂3,4-ethylenedioxyC₆H₃ 1707 4-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 17084-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 1709 4-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 17104-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 1711 4-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 17124-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1713 4-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 17144-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄

TABLE 4

Example Number R¹ R² 1715 Methyl 4-MeOC₆H₄ 1716 ClCH₂ 4-MeOC₆H₄ 1717Cyclopropyl 4-MeOC₆H₄ 1718 Isopropyl 4-MeOC₆H₄ 1719 Ethyl 4-MeOC₆H₄ 1720Cyclopentyl 4-MeOC₆H₄ 1721 Cyclobutyl 4-MeOC₆H₄ 1722 Benzyl 4-MeOC₆H₄1723 n-propyl 4-MeOC₆H₄ 1724 4-ClC₆H₄CH₂ 4-MeOC₆H₄ 1725 3-MeOC₆H₄CH₂4-MeOC₆H₄ 1726 4-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1727 3,4-diMeOC₆H₄CH₂ 4-MeOC₆H₄1728 2,5-diMeOC₆H₄CH₂ 4-MeOC₆H₄ 1729 Methyl 2-MeOC₆H₄ 1730 Methyl3,4-diMeOC₆H₄ 1731 3,4-(OCH₂O)C₆H₄CH₂ 4-MeOC₆H₄ 1732 3-thiophenylCH₂4-MeOC₆H₄ 1733 2-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1734 3,4-diClOC₆H₄CH₂ 4-MeOC₆H₄1735 2,4-diClOC₆H₄CH₂ 4-MeOC₆H₄ 1736 2-ClC₆H₄CH₂ 4-MeOC₆H₄ 1737 H₂NCH₂4-MeOC₆H₄ 1738 HOCH₂NHCH₂CH₂ 4-MeOC₆H₄ 1739 Me₂NCH₂ 4-MeOC₆H₄ 1740PiperazinylCH₂ 4-MeOC₆H₄ 1741 4-Me-piperazinylCH₂ 4-MeOC₆H₄ 17424-HOCH₂CH₂-piperazinylCH₂ 4-MeOC₆H₄ 1743 PiperidinylCH₂ 4-MeOC₆H₄ 17444-NH₂CH₂-piperidinylCH₂ 4-MeOC₆H₄ 1745 CH₃CH₂NHCH₂ 4-MeOC₆H₄ 1746ThiomorpholinylCH₂ 4-MeOC₆H₄ 1747 MorpholinylCH₂ 4-MeOC₆H₄ 1748PyyrolidinylCH₂ 4-MeOC₆H₄ 1749 4-pyridylCH₂NHCH₂ 4-MeOC₆H₄ 17504-CH₃CONHC₆H₄CH₂ 4-MeOC₆H₄ 1751 4-CH₃OCONHC₆H₄CH₂ 4-MeOC₆H₄ 17524-NH₂CH₂CONHC₆H₄CH₂ 4-MeOC₆H₄ 1753 4-Me₂NCH₂CONHC₆H₄CH₂ 4-MeOC₆H₄ 17544-N₃C₆H₄CH₂ 4-MeOC₆H₄ 1755 4-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 1756 C₆H₅NH 4-MeOC₆H₄1757 CH₃CH₂CH₂NH 4-MeOC₆H₄ 1758 4-NH₂C₆H₄CH₂NH 4-MeOC₆H₄ 17594-pyridyCH₂NH 4-MeOC₆H₄ 1760 Methyl 4-HOC₆H₄ 1761 H 4-MeOC₆H₄ 1762Methyl 3-pyridyl 1763 Methyl 4-pyridyl 1764 H 4-pyridyl 1765 Methyl C₆H₅1766 Methyl 4-MeSC₆H₄ 1767 Methyl 4-MeSO₂C₆H₄ 1768 Methyl 4-Me₂NC₆H₄1769 MorpholinylCH₂ 4-Me₂NC₆H₄ 1770 Me₂NCH₂ 4-Me₂NC₆H₄ 1771 Me₂NCH₂4-(piperdinyl)C₆H₄ 1772 Me₂NCH₂ 4-(morpholinyl)C₆H₄ 1773 Me₂NCH₂4-CH₃CH₂OC₆H₄ 1774 Me₂NCH₂ 4-CH₃CH₂CH₂CH₂C₆H₄ 1775 Me₂NCH₂ 4-CH₃CH₂C₆H₄1776 Me₂NCH₂ 4-CH₃CH₂CH₂C₆H₄

What is claimed is:
 1. A compound according to the formula:

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein: X is selected from the group consisting of O and S; R¹ is NHR₄;R⁴ is NR³R^(3a); R^(3a) is H or C₁₋₄ alkyl; R³ is COR⁵; R⁵ is phenyl;and R² is phenyl substituted with C₁₋₄ alkoxy.
 2. A compound accordingto claim 1, wherein the compound is3-(4-methoxyphenyl)-5-(2-benzoylhydrazinecarboxamido)indeno[1,2-c]pyrazol-4-one.3. A pharmaceutical composition comprising a pharmaceutically acceptablecarrier and a therapeutically effective amount of a compound of thefollowing formula:

or a stereoisomer or pharmaceutically acceptable salt form thereof,wherein: X is selected from the group consisting of O and S; R¹ is NHR₄;R⁴ is NR³R^(3a); R^(3a) is H or C₁₋₄ alkyl; R³ is COR⁵; R⁵ is phenyl;and R² is phenyl substituted with C₁₋₄ alkoxy.
 4. A method of treatingcancer and proliferative diseases comprising: administering to a host inneed of such treatment a therapeutically effective amount of a compoundof the following formula:

or a pharmaceutically acceptable salt or prodrug form thereof, wherein:X is selected from the group consisting of O and S; R¹ is NHR₄; R⁴ isNR³R^(3a); R^(3a) is H or C₁₋₄ alkyl; R³ is COR⁵; R⁵ is phenyl; and R²is phenyl substituted with C₁₋₄ alkoxy.